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Current Pharmaceutical Design

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ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

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Review Article

Lipophilic Guanylhydrazone Analogues as Promising Trypanocidal Agents: An Extended SAR Study

Author(s): Vasiliki Pardali, Erofili Giannakopoulou, Dimitrios-Ilias Balourdas, Vassilios Myrianthopoulos, Martin C. Taylor, Marina Šekutor, Kata Mlinarić-Majerski, John M. Kelly and Grigoris Zoidis*

Volume 26, Issue 8, 2020

Page: [838 - 866] Pages: 29

DOI: 10.2174/1381612826666200210150127

Price: $65

Abstract

In this report, we extend the SAR analysis of a number of lipophilic guanylhydrazone analogues with respect to in vitro growth inhibition of Trypanosoma brucei and Trypanosoma cruzi. Sleeping sickness and Chagas disease, caused by the tropical parasites T. brucei and T. cruzi, constitute a significant socioeconomic burden in low-income countries of sub-Saharan Africa and Latin America, respectively. Drug development is underfunded. Moreover, current treatments are outdated and difficult to administer, while drug resistance is an emerging concern. The synthesis of adamantane-based compounds that have potential as antitrypanosomal agents is extensively reviewed. The critical role of the adamantane ring was further investigated by synthesizing and testing a number of novel lipophilic guanylhydrazones. The introduction of hydrophobic bulky substituents onto the adamantane ring generated the most active analogues, illustrating the synergistic effect of the lipophilic character of the C1 side chain and guanylhydrazone moiety on trypanocidal activity. The n-decyl C1-substituted compound G8 proved to be the most potent adamantane derivative against T. brucei with activity in the nanomolar range (EC50=90 nM). Molecular simulations were also performed to better understand the structure-activity relationships between the studied guanylhydrazone analogues and their potential enzyme target.

Keywords: Adamantane, S-adenosylmethionine decarboxylase (AdoMetDC), guanylhydrazones, structure-activity relationships, trypanocidal agents, kernel-based partial least squares regression, szmap, hydration analysis, docking-scoring calculations.

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[1]
Mackey TK, Liang BA, Cuomo R, Hafen R, Brouwer KC, Lee DE. Emerging and reemerging neglected tropical diseases: a review of key characteristics, risk factors, and the policy and innovation environment. Clin Microbiol Rev 2014; 27(4): 949-79.
[http://dx.doi.org/10.1128/CMR.00045-14] [PMID: 25278579]
[2]
Addisu A, Adriaensen W, Balew A, et al. Ethiopia SORT IT Neglected Tropical Diseases Group. Neglected tropical diseases and the sustainable development goals: an urgent call for action from the front line. BMJ Glob Health 2019; 4(1) e001334
[http://dx.doi.org/10.1136/bmjgh-2018-001334] [PMID: 30899568]
[3]
Peeling RW, Boeras DI, Nkengasong J. Re-imagining the future of diagnosis of neglected tropical diseases. Comput Struct Biotechnol J 2017; 15: 271-4.
[http://dx.doi.org/10.1016/j.csbj.2017.02.003] [PMID: 28352456]
[4]
Mitra AK, Mawson AR. Neglected tropical diseases: epidemiology and global burden. Trop Med Infect Dis 2017; 2(3): 36.
[http://dx.doi.org/10.3390/tropicalmed2030036] [PMID: 30270893]
[5]
Varikuti S, Jha BK, Volpedo G, et al. Host-directed drug therapies for neglected tropical diseases caused by protozoan parasites. Front Microbiol 2018; 9: 2655.
[http://dx.doi.org/10.3389/fmicb.2018.02655] [PMID: 30555425]
[6]
Hotez PJ, Kamath A. Neglected tropical diseases in sub-saharan Africa: review of their prevalence, distribution, and disease burden. PLoS Negl Trop Dis 2009; 3(8) e412
[http://dx.doi.org/10.1371/journal.pntd.0000412] [PMID: 19707588]
[7]
Kennedy PGE. Update on human African trypanosomiasis (sleeping sickness). J Neurol 2019; 266(9): 2334-7.
[http://dx.doi.org/10.1007/s00415-019-09425-7] [PMID: 31209574]
[8]
World Health Organization Sleeping Sickness Available at:. https://www.who.int/news-room/fact-sheets/detail/trypanosomiasis-human-african-(sleeping-sickness)
[9]
Bottieau E, Clerinx J. Human African trypanosomiasis: progress and stagnation. Infect Dis Clin North Am 2019; 33(1): 61-77.
[http://dx.doi.org/10.1016/j.idc.2018.10.003] [PMID: 30712768]
[10]
Büscher P, Cecchi G, Jamonneau V, Priotto G. Human African trypanosomiasis. Lancet 2017; 390(10110): 2397-409.
[http://dx.doi.org/10.1016/S0140-6736(17)31510-6] [PMID: 28673422]
[11]
Malvy D, Chappuis F. Sleeping sickness. Clin Microbiol Infect 2011; 17(7): 986-95.
[http://dx.doi.org/10.1111/j.1469-0691.2011.03536.x] [PMID: 21722252]
[12]
Geiger A, Ravel S, Mateille T, et al. Vector competence of Glossina palpalis gambiensis for Trypanosoma brucei s.l. and genetic diversity of the symbiont Sodalis glossinidius. Mol Biol Evol 2007; 24(1): 102-9.
[http://dx.doi.org/10.1093/molbev/msl135] [PMID: 17012373]
[13]
Geiger A, Cuny G, Frutos R. Two Tsetse fly species, Glossina palpalis gambiensis and Glossina morsitans morsitans, carry genetically distinct populations of the secondary symbiont Sodalis glossinidius. Appl Environ Microbiol 2005; 71(12): 8941-3.
[http://dx.doi.org/10.1128/AEM.71.12.8941-8943.2005] [PMID: 16332895]
[14]
Steverding D. The history of African trypanosomiasis. Parasit Vectors 2008; 1(1): 3.
[http://dx.doi.org/10.1186/1756-3305-1-3] [PMID: 18275594]
[15]
Welburn SC, Molyneux DH, Maudlin I. Beyond tsetse--implications for research and control of human African trypanosomiasis epidemics. Trends Parasitol 2016; 32(3): 230-41.
[http://dx.doi.org/10.1016/j.pt.2015.11.008] [PMID: 26826783]
[16]
Kennedy PGE, Rodgers J. Clinical and neuropathogenetic aspects of human African trypanosomiasis. Front Immunol 2019; 10: 39.
[http://dx.doi.org/10.3389/fimmu.2019.00039] [PMID: 30740102]
[17]
Franco JR, Cecchi G, Priotto G, et al. Monitoring the elimination of human African trypanosomiasis: Update to 2016. PLoS Negl Trop Dis 2018; 12(12) e0006890
[http://dx.doi.org/10.1371/journal.pntd.0006890] [PMID: 30521525]
[18]
Franco JR, Simarro PP, Diarra A, Jannin JG. Epidemiology of human African trypanosomiasis. Clin Epidemiol 2014; 6: 257-75.
[PMID: 25125985]
[19]
Lindner AK, Priotto G. The unknown risk of vertical transmission in sleeping sickness--a literature review. PLoS Negl Trop Dis 2010; 4(12) e783
[http://dx.doi.org/10.1371/journal.pntd.0000783] [PMID: 21200416]
[20]
Gaillot K, Lauvin MA, Cottier JP. Vertical transmission of human African trypanosomiasis: Clinical evolution and brain MRI of a mother and her son. PLoS Negl Trop Dis 2017; 11(7) e0005642
[http://dx.doi.org/10.1371/journal.pntd.0005642] [PMID: 28750004]
[21]
Biteau N, Asencio C, Izotte J, et al. Trypanosoma brucei gambiense Infections in mice lead to tropism to the reproductive organs, and horizontal and vertical transmission. PLoS Negl Trop Dis 2016; 10(1) e0004350
[http://dx.doi.org/10.1371/journal.pntd.0004350] [PMID: 26735855]
[22]
Rocha G, Martins A, Gama G, Brandão F, Atouguia J. Possible cases of sexual and congenital transmission of sleeping sickness. Lancet 2004; 363(9404): 247.
[http://dx.doi.org/10.1016/S0140-6736(03)15345-7] [PMID: 14738812]
[23]
Migchelsen SJ, Büscher P, Hoepelman AI, Schallig HD, Adams ER. Human African trypanosomiasis: a review of non-endemic cases in the past 20 years. Int J Infect Dis 2011; 15(8): e517-24.
[http://dx.doi.org/10.1016/j.ijid.2011.03.018] [PMID: 21683638]
[24]
Kennedy PGE. Clinical features, diagnosis, and treatment of human African trypanosomiasis (sleeping sickness). Lancet Neurol 2013; 12(2): 186-94.
[http://dx.doi.org/10.1016/S1474-4422(12)70296-X] [PMID: 23260189]
[25]
Chappuis F, Loutan L, Simarro P, Lejon V, Büscher P. Options for field diagnosis of human african trypanosomiasis. Clin Microbiol Rev 2005; 18(1): 133-46.
[http://dx.doi.org/10.1128/CMR.18.1.133-146.2005] [PMID: 15653823]
[26]
Kennedy PGE. Human African trypanosomiasis of the CNS: current issues and challenges. J Clin Invest 2004; 113(4): 496-504.
[http://dx.doi.org/10.1172/JCI200421052] [PMID: 14966556]
[27]
Checchi F, Funk S, Chandramohan D, Haydon DT, Chappuis F. Updated estimate of the duration of the meningo-encephalitic stage in gambiense human African trypanosomiasis. BMC Res Notes 2015; 8: 292.
[http://dx.doi.org/10.1186/s13104-015-1244-3] [PMID: 26140922]
[28]
Mogk S, Boßelmann CM, Mudogo CN, Stein J, Wolburg H, Duszenko M. African trypanosomes and brain infection - the unsolved question. Biol Rev Camb Philos Soc 2017; 92(3): 1675-87.
[http://dx.doi.org/10.1111/brv.12301] [PMID: 27739621]
[29]
Njamnshi AK, Gettinby G, Kennedy PGE. The challenging problem of disease staging in human African trypanosomiasis (sleeping sickness): a new approach to a circular question. Trans R Soc Trop Med Hyg 2017; 111(5): 199-203.
[http://dx.doi.org/10.1093/trstmh/trx034] [PMID: 28957467]
[30]
Bonnet J, Boudot C, Courtioux B. Overview of the diagnostic methods used in the field for human African trypanosomiasis: what could change in the next years? BioMed Res Int 2015; 2015 583262
[http://dx.doi.org/10.1155/2015/583262] [PMID: 26504815]
[31]
Büscher P, Mertens P, Leclipteux T, et al. Sensitivity and specificity of HAT Sero-K-SeT, a rapid diagnostic test for serodiagnosis of sleeping sickness caused by Trypanosoma brucei gambiense: a case-control study. Lancet Glob Health 2014; 2(6): e359-63.
[http://dx.doi.org/10.1016/S2214-109X(14)70203-7] [PMID: 25103304]
[32]
Ponte-Sucre A. An overview of trypanosoma brucei infections: an intense host-parasite interaction. Front Microbiol 2016; 7: 2126.
[http://dx.doi.org/10.3389/fmicb.2016.02126] [PMID: 28082973]
[33]
Kato CD, Matovu E, Mugasa CM, Nanteza A, Alibu VP. The role of cytokines in the pathogenesis and staging of Trypanosoma brucei rhodesiense sleeping sickness. Allergy Asthma Clin Immunol 2016; 12: 4.
[http://dx.doi.org/10.1186/s13223-016-0113-5] [PMID: 26807135]
[34]
Barrett MP, Boykin DW, Brun R, Tidwell RR. Human African trypanosomiasis: pharmacological re-engagement with a neglected disease. Br J Pharmacol 2007; 152(8): 1155-71.
[http://dx.doi.org/10.1038/sj.bjp.0707354] [PMID: 17618313]
[35]
Steverding D. Sleeping sickness and nagana disease caused by Trypanosoma brucei arthropod borne diseases. Cham: Springer 2017; pp. 277-97.
[http://dx.doi.org/10.1007/978-3-319-13884-8_18]
[36]
Babokhov P, Sanyaolu AO, Oyibo WA, Fagbenro-Beyioku AF, Iriemenam NC. A current analysis of chemotherapy strategies for the treatment of human African trypanosomiasis. Pathog Glob Health 2013; 107(5): 242-52.
[http://dx.doi.org/10.1179/2047773213Y.0000000105] [PMID: 23916333]
[37]
Thomas JA, Baker N, Hutchinson S, et al. Insights into antitrypanosomal drug mode-of-action from cytology-based profiling. PLoS Negl Trop Dis 2018; 12(11) e0006980
[http://dx.doi.org/10.1371/journal.pntd.0006980] [PMID: 30475806]
[38]
Zhang Y, Li Z, Pilch DS, Leibowitz MJ. Pentamidine inhibits catalytic activity of group I intron Ca.LSU by altering RNA folding. Nucleic Acids Res 2002; 30(13): 2961-71.
[http://dx.doi.org/10.1093/nar/gkf394] [PMID: 12087182]
[39]
Jacobs RT, Nare B, Phillips MA. State of the art in African trypanosome drug discovery. Curr Top Med Chem 2011; 11(10): 1255-74.
[http://dx.doi.org/10.2174/156802611795429167] [PMID: 21401507]
[40]
Denise H, Barrett MP. Uptake and mode of action of drugs used against sleeping sickness. Biochem Pharmacol 2001; 61(1): 1-5.
[http://dx.doi.org/10.1016/S0006-2952(00)00477-9] [PMID: 11137702]
[41]
Franco JR, Simarro PP, Diarra A, Ruiz-Postigo JA, Samo M, Jannin JG. Monitoring the use of nifurtimox-eflornithine combination therapy (NECT) in the treatment of second stage gambiense human African trypanosomiasis. Res Rep Trop Med 2012; 3: 93-101.
[http://dx.doi.org/10.2147/RRTM.S34399] [PMID: 30100776]
[42]
Eperon G, Balasegaram M, Potet J, Mowbray C, Valverde O, Chappuis F. Treatment options for second-stage gambiense human African trypanosomiasis. Expert Rev Anti Infect Ther 2014; 12(11): 1407-17.
[http://dx.doi.org/10.1586/14787210.2014.959496] [PMID: 25204360]
[43]
Kansiime F, Adibaku S, Wamboga C, et al. A multicentre, randomised, non-inferiority clinical trial comparing a nifurtimox-eflornithine combination to standard eflornithine monotherapy for late stage Trypanosoma brucei gambiense human African trypanosomiasis in Uganda. Parasit Vectors 2018; 11(1): 105.
[http://dx.doi.org/10.1186/s13071-018-2634-x] [PMID: 29471865]
[44]
Deeks ED. Fexinidazole: first global approval. Drugs 2019; 79(2): 215-20.
[http://dx.doi.org/10.1007/s40265-019-1051-6] [PMID: 30635838]
[45]
Chappuis F. Oral fexinidazole for human African trypanosomiasis. Lancet 2018; 391(10116): 100-2.
[http://dx.doi.org/10.1016/S0140-6736(18)30019-9] [PMID: 29353603]
[46]
Baker CH, Welburn SC. The long wait for a new drug for Human African trypanosomiasis. Trends Parasitol 2018; 34(10): 818-27.
[http://dx.doi.org/10.1016/j.pt.2018.08.006] [PMID: 30181071]
[47]
Nagle AS, Khare S, Kumar AB, et al. Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis. Chem Rev 2014; 114(22): 11305-47.
[http://dx.doi.org/10.1021/cr500365f] [PMID: 25365529]
[48]
Steketee PC, Vincent IM, Achcar F, et al. Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei. PLoS Negl Trop Dis 2018; 12(5) e0006450
[http://dx.doi.org/10.1371/journal.pntd.0006450] [PMID: 29758036]
[49]
Lewis MD, Francisco AF, Jayawardhana S, Langston H, Taylor MC, Kelly JM. Imaging the development of chronic Chagas disease after oral transmission. Sci Rep 2018; 8(1): 11292.
[http://dx.doi.org/10.1038/s41598-018-29564-7] [PMID: 30050153]
[50]
World Health Organization. American-trypanosomiasis. Availabe at:. https://www.who.int/en/news-room/fact-sheets/detail/chagas-disease-(american-trypanosomiasis)
[51]
Pérez-Molina JA, Perez AM, Norman FF, Monge-Maillo B, López-Vélez R. Old and new challenges in Chagas disease. Lancet Infect Dis 2015; 15(11): 1347-56.
[http://dx.doi.org/10.1016/S1473-3099(15)00243-1] [PMID: 26231478]
[52]
Stevens L, Dorn PL, Schmidt JO, Klotz JH, Lucero D, Klotz SA. Kissing bugs. The vectors of Chagas. Adv Parasitol 2011; 75: 169-92.
[http://dx.doi.org/10.1016/B978-0-12-385863-4.00008-3] [PMID: 21820556]
[53]
Rassi A Jr, Rassi A, Marin-Neto JA. Chagas disease. Lancet 2010; 375(9723): 1388-402.
[http://dx.doi.org/10.1016/S0140-6736(10)60061-X] [PMID: 20399979]
[54]
Rajão MA, Furtado C, Alves CL, et al. Unveiling benznidazole’s mechanism of action through overexpression of DNA repair proteins in Trypanosoma cruzi. Environ Mol Mutagen 2014; 55(4): 309-21.
[http://dx.doi.org/10.1002/em.21839] [PMID: 24347026]
[55]
Bermudez J, Davies C, Simonazzi A, Real JP, Palma S. Current drug therapy and pharmaceutical challenges for Chagas disease. Acta Trop 2016; 156: 1-16.
[http://dx.doi.org/10.1016/j.actatropica.2015.12.017] [PMID: 26747009]
[56]
Field MC, Horn D, Fairlamb AH, et al. Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need. Nat Rev Microbiol 2017; 15(7): 447.
[http://dx.doi.org/10.1038/nrmicro.2017.69] [PMID: 28579611]
[57]
Stich A, Ponte-Sucre A, Holzgrabe U. Do we need new drugs against human African trypanosomiasis? Lancet Infect Dis 2013; 13(9): 733-4.
[http://dx.doi.org/10.1016/S1473-3099(13)70191-9] [PMID: 23969207]
[58]
Willert E, Phillips MA. Regulation and function of polyamines in African trypanosomes. Trends Parasitol 2012; 28(2): 66-72.
[http://dx.doi.org/10.1016/j.pt.2011.11.001] [PMID: 22192816]
[59]
Phillips MA. Polyamines in protozoan pathogens. J Biol Chem 2018; 293(48): 18746-56.
[http://dx.doi.org/10.1074/jbc.TM118.003342] [PMID: 30333232]
[60]
Müller S, Coombs GH, Walter RD. Targeting polyamines of parasitic protozoa in chemotherapy. Trends Parasitol 2001; 17(5): 242-9.
[http://dx.doi.org/10.1016/S1471-4922(01)01908-0] [PMID: 11323309]
[61]
Keiser J, Stich A, Burri C. New drugs for the treatment of human African trypanosomiasis: research and development. Trends Parasitol 2001; 17(1): 42-9.
[http://dx.doi.org/10.1016/S1471-4922(00)01829-8] [PMID: 11137740]
[62]
Heby O, Persson L, Rentala M. Targeting the polyamine biosynthetic enzymes: a promising approach to therapy of African sleeping sickness, Chagas’ disease, and leishmaniasis. Amino Acids 2007; 33(2): 359-66.
[http://dx.doi.org/10.1007/s00726-007-0537-9] [PMID: 17610127]
[63]
Birkholtz LM, Williams M, Niemand J, Louw AI, Persson L, Heby O. Polyamine homoeostasis as a drug target in pathogenic protozoa: peculiarities and possibilities. Biochem J 2011; 438(2): 229-44.
[http://dx.doi.org/10.1042/BJ20110362] [PMID: 21834794]
[64]
Smithson DC, Lee J, Shelat AA, Phillips MA, Guy RK. Discovery of potent and selective inhibitors of Trypanosoma brucei ornithine decarboxylase. J Biol Chem 2010; 285(22): 16771-81.
[http://dx.doi.org/10.1074/jbc.M109.081588] [PMID: 20220141]
[65]
Tekwani BL, Bacchi CJ, Secrist JA III, Pegg AE. Irreversible inhibition of S-adenosylmethionine decarboxylase of Trypanosoma brucei brucei by S-adenosylmethionine analogues. Biochem Pharmacol 1992; 44(5): 905-11.
[http://dx.doi.org/10.1016/0006-2952(92)90122-Y] [PMID: 1530659]
[66]
Hirth B, Barker RH Jr, Celatka CA, et al. Discovery of new S-adenosylmethionine decarboxylase inhibitors for the treatment of Human African Trypanosomiasis (HAT). Bioorg Med Chem Lett 2009; 19(11): 2916-9.
[http://dx.doi.org/10.1016/j.bmcl.2009.04.096] [PMID: 19419862]
[67]
Barker RH Jr, Liu H, Hirth B, et al. Novel S-adenosylmethionine decarboxylase inhibitors for the treatment of human African trypanosomiasis. Antimicrob Agents Chemother 2009; 53(5): 2052-8.
[http://dx.doi.org/10.1128/AAC.01674-08] [PMID: 19289530]
[68]
Bacchi CJ, Barker RH Jr, Rodriguez A, et al. Trypanocidal activity of 8-methyl-5′-[(Z)-4-aminobut-2-enyl]-(methylamino)adenosine (Genz-644131), an adenosylmethionine decarboxylase inhibitor. Antimicrob Agents Chemother 2009; 53(8): 3269-72.
[http://dx.doi.org/10.1128/AAC.00076-09] [PMID: 19451291]
[69]
Volkov OA, Cosner CC, Brockway AJ, et al. Identification of Trypanosoma brucei AdoMetDC inhibitors using a high-throughput mass spectrometry-based assay. ACS Infect Dis 2017; 3(7): 512-26.
[http://dx.doi.org/10.1021/acsinfecdis.7b00022] [PMID: 28350440]
[70]
Volkov OA, Brockway AJ, Wring SA, et al. Species-selective pyrimidineamine inhibitors of Trypanosoma brucei S-adenosylmethionine decarboxylase. J Med Chem 2018; 61(3): 1182-203.
[http://dx.doi.org/10.1021/acs.jmedchem.7b01654] [PMID: 29271204]
[71]
Brockway AJ, Volkov OA, Cosner CC, et al. Synthesis and evaluation of analogs of 5′-(((Z)-4-amino-2-butenyl)methylamino)-5′-deoxyadenosine (MDL 73811, or AbeAdo) - An inhibitor of S-adenosylmethionine decarboxylase with antitrypanosomal activity. Bioorg Med Chem 2017; 25(20): 5433-40.
[http://dx.doi.org/10.1016/j.bmc.2017.07.063] [PMID: 28807574]
[72]
Velez N, Brautigam CA, Phillips MA. Trypanosoma brucei S-adenosylmethionine decarboxylase N terminus is essential for allosteric activation by the regulatory subunit prozyme. J Biol Chem 2013; 288(7): 5232-40.
[http://dx.doi.org/10.1074/jbc.M112.442475] [PMID: 23288847]
[73]
Lamoureux G, Artavia G. Use of the adamantane structure in medicinal chemistry. Curr Med Chem 2010; 17(26): 2967-78.
[http://dx.doi.org/10.2174/092986710792065027] [PMID: 20858176]
[74]
Wanka L, Iqbal K, Schreiner PR. The lipophilic bullet hits the targets: medicinal chemistry of adamantane derivatives. Chem Rev 2013; 113(5): 3516-604.
[http://dx.doi.org/10.1021/cr100264t] [PMID: 23432396]
[75]
Van der Schyf CJ, Geldenhuys WJ. Polycyclic compounds: ideal drug scaffolds for the design of multiple mechanism drugs? Neurotherapeutics 2009; 6(1): 175-86.
[http://dx.doi.org/10.1016/j.nurt.2008.10.037] [PMID: 19110208]
[76]
Stockdale TP, Williams CM. Pharmaceuticals that contain polycyclic hydrocarbon scaffolds. Chem Soc Rev 2015; 44(21): 7737-63.
[http://dx.doi.org/10.1039/C4CS00477A] [PMID: 26171466]
[77]
Štimac A, Šekutor M, Mlinarić-Majerski K, Frkanec L, Frkanec R. Adamantane in drug delivery systems and surface recognition. Molecules 2017; 22(2) E297
[http://dx.doi.org/10.3390/molecules22020297] [PMID: 28212339]
[78]
Geldenhuys WJ, Malan SF, Bloomquist JR, Marchand AP, Van der Schyf CJ. Pharmacology and structure-activity relationships of bioactive polycyclic cage compounds: a focus on pentacycloundecane derivatives. Med Res Rev 2005; 25(1): 21-48.
[http://dx.doi.org/10.1002/med.20013] [PMID: 15389731]
[79]
Liu J, Obando D, Liao V, Lifa T, Codd R. The many faces of the adamantyl group in drug design. Eur J Med Chem 2011; 46(6): 1949-63.
[http://dx.doi.org/10.1016/j.ejmech.2011.01.047] [PMID: 21354674]
[80]
Grillaud M, Bianco A. Multifunctional adamantane derivatives as new scaffolds for the multipresentation of bioactive peptides. J Pept Sci 2015; 21(5): 330-45.
[http://dx.doi.org/10.1002/psc.2719] [PMID: 25448731]
[81]
Horvat S, Mlinarić-Majerski K, Glavas-Obrovac L, et al. Tumor-cell-targeted methionine-enkephalin analogues containing unnatural amino acids: design, synthesis, and in vitro antitumor activity. J Med Chem 2006; 49(11): 3136-42.
[http://dx.doi.org/10.1021/jm051026+] [PMID: 16722632]
[82]
Li Z, Khaliq M, Zhou Z, Post CB, Kuhn RJ, Cushman M. Design, synthesis, and biological evaluation of antiviral agents targeting flavivirus envelope proteins. J Med Chem 2008; 51(15): 4660-71.
[http://dx.doi.org/10.1021/jm800412d] [PMID: 18610998]
[83]
Ajdačić V, Senerovic L, Vranić M, et al. Synthesis and evaluation of thiophene-based guanylhydrazones (iminoguanidines) efficient against panel of voriconazole-resistant fungal isolates. Bioorg Med Chem 2016; 24(6): 1277-91.
[http://dx.doi.org/10.1016/j.bmc.2016.01.058] [PMID: 26867487]
[84]
Ajdačić V, Lazić J, Mojičević M, Šegan S, Nikodinović-Runić J, Opsenica I. Antibacterial and antifungal properties of guanylhydrazones. J Serb Chem Soc 2017; 82(6): 641-9.
[http://dx.doi.org/10.2298/JSC170213033A]
[85]
Gadad AK, Mahajanshetti CS, Nimbalkar S, Raichurkar A. Synthesis and antibacterial activity of some 5-guanylhydrazone/thiocyanato-6-arylimidazo[2,1-b]-1,3, 4-thiadiazole-2-sulfonamide derivatives. Eur J Med Chem 2000; 35(9): 853-7.
[http://dx.doi.org/10.1016/S0223-5234(00)00166-5] [PMID: 11006486]
[86]
Bairwa R, Kakwani M, Tawari NR, et al. Novel molecular hybrids of cinnamic acids and guanylhydrazones as potential antitubercular agents. Bioorg Med Chem Lett 2010; 20(5): 1623-5.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.031] [PMID: 20138519]
[87]
Silva FP, Dantas BB, Faheina Martins GV, de Araújo DA, Vasconcellos ML. Synthesis and anticancer activities of novel guanylhydrazone and aminoguanidine tetrahydropyran derivatives. Molecules 2016; 21(6) E671
[http://dx.doi.org/10.3390/molecules21060671] [PMID: 27338323]
[88]
Andreani A, Burnelli S, Granaiola M, et al. Synthesis and antitumor activity of guanylhydrazones from 6-(2,4-dichloro-5-nitrophenyl)imidazo[2,1-b]thiazoles and 6-pyridylimidazo[2,1-b]thiazoles(1). J Med Chem 2006; 49(26): 7897-901.
[http://dx.doi.org/10.1021/jm061077m] [PMID: 17181173]
[89]
Kamal A, Kashi Reddy M, Viswanath A. The design and development of imidazothiazole-chalcone derivatives as potential anticancer drugs. Expert Opin Drug Discov 2013; 8(3): 289-304.
[http://dx.doi.org/10.1517/17460441.2013.758630] [PMID: 23317445]
[90]
de Oliveira C Brum J, Neto DCF, de Almeida JSFD, et al. Synthesis of new quinoline-piperonal hybrids as potential drugs against Alzheimer’s disease. Int J Mol Sci 2019; 20(16): 3944.
[http://dx.doi.org/10.3390/ijms20163944] [PMID: 31416113]
[91]
Neto DCF, de Souza Ferreira M, da Conceição Petronilho E, et al. A new guanylhydrazone derivative as a potential acetylcholinesterase inhibitor for alzheimer’s disease: synthesis, molecular docking, biological evaluation and kinetic studies by nuclear magnetic resonance. RSC Advances 2017; 7: 33944-52.
[http://dx.doi.org/10.1039/C7RA04180B]
[92]
Soll RM, Lu T, Tomczuk B, et al. Amidinohydrazones as guanidine bioisosteres: application to a new class of potent, selective and orally bioavailable, non-amide-based small-molecule thrombin inhibitors. Bioorg Med Chem Lett 2000; 10(1): 1-4.
[http://dx.doi.org/10.1016/S0960-894X(99)00632-0] [PMID: 10636229]
[93]
Barron S, Lewis B, Wellmann K, et al. Polyamine modulation of NMDARs as a mechanism to reduce effects of alcohol dependence. Recent Patents CNS Drug Discov 2012; 7(2): 129-44.
[http://dx.doi.org/10.2174/157488912800673128] [PMID: 22574674]
[94]
Kathuria D, Chourasiya SS, Wani AA, Singh M, Sahoo SC, Bharatam PV. Geometrical isomerism in guanabenz free base: synthesis, characterization, crystal structure, and theoretical studies. Cryst Growth Des 2019; 19(6): 3183-91.
[http://dx.doi.org/10.1021/acs.cgd.9b00026]
[95]
Wang J, Grishin AV, Ford HR. Experimental anti-inflammatory drug semapimod inhibits TLR signaling by targeting the TLR chaperone gp96. J Immunol 2016; 196(12): 5130-7.
[http://dx.doi.org/10.4049/jimmunol.1502135] [PMID: 27194788]
[96]
Pardali V, Giannakopoulou E, Konstantinidi A, Kolocouris A, Zoidis G. 1,2-Annulated adamantane heterocyclic derivatives as anti-influenza a virus agents. Croat Chem Acta 2019; 92(2): 211-28.
[http://dx.doi.org/10.5562/cca3540]
[97]
Fytas G, Zoidis G, Taylor MC, Kelly JM, Tsatsaroni A, Tsotinis A. Novel 2,6-diketopiperazine-derived acetohydroxamic acids as promising anti-Trypanosoma brucei agents. Future Med Chem 2019; 11(11): 1259-66.
[http://dx.doi.org/10.4155/fmc-2018-0599] [PMID: 31161793]
[98]
Kolocouris N, Zoidis G, Foscolos GB, et al. Design and synthesis of bioactive adamantane spiro heterocycles. Bioorg Med Chem Lett 2007; 17(15): 4358-62.
[http://dx.doi.org/10.1016/j.bmcl.2007.04.108] [PMID: 17588747]
[99]
Zoidis G, Tsotinis A, Kolocouris N, et al. Design and synthesis of bioactive 1,2-annulated adamantane derivatives. Org Biomol Chem 2008; 6(17): 3177-85.
[http://dx.doi.org/10.1039/b804907f] [PMID: 18698478]
[100]
Zoidis G, Kolocouris N, Naesens L, De Clercq E. Design and synthesis of 1,2-annulated adamantane piperidines with anti-influenza virus activity. Bioorg Med Chem 2009; 17(4): 1534-41.
[http://dx.doi.org/10.1016/j.bmc.2009.01.009] [PMID: 19195900]
[101]
Zoidis G, Kolocouris N, Kelly JM, Prathalingam SR, Naesens L, De Clercq E. Design and synthesis of bioactive adamantanaminoalcohols and adamantanamines. Eur J Med Chem 2010; 45(11): 5022-30.
[http://dx.doi.org/10.1016/j.ejmech.2010.08.009] [PMID: 20805012]
[102]
Fytas C, Zoidis G, Tzoutzas N, Taylor MC, Fytas G, Kelly JM. Novel lipophilic acetohydroxamic acid derivatives based on conformationally constrained spiro carbocyclic 2,6-diketopiperazine scaffolds with potent trypanocidal activity. J Med Chem 2011; 54(14): 5250-4.
[http://dx.doi.org/10.1021/jm200217m] [PMID: 21542562]
[103]
Zoidis G, Tsotinis A, Tsatsaroni A, et al. Lipophilic conformationally constrained spiro carbocyclic 2,6-diketopiperazine-1-acetohydroxamic acid analogues as trypanocidal and leishmanicidal agents: An extended SAR study. Chem Biol Drug Des 2018; 91(2): 408-21.
[http://dx.doi.org/10.1111/cbdd.13088] [PMID: 28834291]
[104]
Ulrich P, Cerami A. Trypanocidal 1,3-arylene diketone bis(guanylhydrazone)s. Structure-activity relationships among substituted and heterocyclic analogues. J Med Chem 1984; 27(1): 35-40.
[http://dx.doi.org/10.1021/jm00367a007] [PMID: 6690682]
[105]
Bitonti AJ, Dumont JA, McCann PP. Characterization of Trypanosoma brucei brucei S-adenosyl-L-methionine decarboxylase and its inhibition by Berenil, pentamidine and methylglyoxal bis(guanylhydrazone). Biochem J 1986; 237(3): 685-9.
[http://dx.doi.org/10.1042/bj2370685] [PMID: 3800910]
[106]
Sundberg RJ, Dahlhausen DJ, Manikumar G, et al. Cationic antiprotozoal drugs. Trypanocidal activity of 2-(4′-formylphenyl)imidazo[1,2-a]pyridinium guanylhydrazones and related derivatives of quaternary heteroaromatic compounds. J Med Chem 1990; 33(1): 298-307.
[http://dx.doi.org/10.1021/jm00163a049] [PMID: 2296025]
[107]
Messeder JC, Tinoco LW, Figueroa-Villar JD, Souza EM, Santa Rita R, de Castro SL. Aromatic guanyl hydrazones: Synthesis, structural studies and in vitro activity against trypanosoma cruzi. Bioorg Med Chem Lett 1995; 5(24): 3079-84.
[http://dx.doi.org/10.1016/0960-894X(95)00541-5]
[108]
Bacchi CJ, Brun R, Croft SL, Alicea K, Bühler Y. In vivo trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob Agents Chemother 1996; 40(6): 1448-53.
[http://dx.doi.org/10.1128/AAC.40.6.1448] [PMID: 8726018]
[109]
Brun R, Bühler Y, Sandmeier U, et al. In vitro trypanocidal activities of new S-adenosylmethionine decarboxylase inhibitors. Antimicrob Agents Chemother 1996; 40(6): 1442-7.
[http://dx.doi.org/10.1128/AAC.40.6.1442] [PMID: 8726017]
[110]
Borges MN, Messeder JC, Figueroa-Villar JD. Synthesis, anti-Trypanosoma cruzi activity and micelle interaction studies of bisguanylhydrazones analogous to pentamidine. Eur J Med Chem 2004; 39(11): 925-9.
[http://dx.doi.org/10.1016/j.ejmech.2004.07.001] [PMID: 15501541]
[111]
Ellis S, Sexton DW, Steverding D. Trypanotoxic activity of thiosemicarbazone iron chelators. Exp Parasitol 2015; 150: 7-12.
[http://dx.doi.org/10.1016/j.exppara.2015.01.004] [PMID: 25595343]
[112]
Papanastasiou I, Tsotinis A, Kolocouris N, Prathalingam SR, Kelly JM. Design, synthesis, and trypanocidal activity of new aminoadamantane derivatives. J Med Chem 2008; 51(5): 1496-500.
[http://dx.doi.org/10.1021/jm7014292] [PMID: 18281929]
[113]
Papanastasiou I, Tsotinis A, Zoidis G, Kolocouris N, Prathalingam SR, Kelly JM. Design and synthesis of Trypanosoma brucei active 1-alkyloxy and 1-benzyloxyadamantano 2-guanylhydrazones. ChemMedChem 2009; 4(7): 1059-62.
[http://dx.doi.org/10.1002/cmdc.200900019] [PMID: 19422003]
[114]
Šekutor M, Mlinarić-Majerski K, Hrenar T, Tomić S, Primožič I. Adamantane-substituted guanylhydrazones: novel inhibitors of butyrylcholinesterase. Bioorg Chem 2012; 41-42: 28-34.
[http://dx.doi.org/10.1016/j.bioorg.2012.01.004] [PMID: 22336689]
[115]
Hirumi H, Hirumi K. Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers. J Parasitol 1989; 75(6): 985-9.
[http://dx.doi.org/10.2307/3282883] [PMID: 2614608]
[116]
Taylor MC, McLatchie AP, Kelly JM. Evidence that transport of iron from the lysosome to the cytosol in African trypanosomes is mediated by a mucolipin orthologue. Mol Microbiol 2013; 89(3): 420-32.
[http://dx.doi.org/10.1111/mmi.12285] [PMID: 23750752]
[117]
Kendall G, Wilderspin AF, Ashall F, Miles MA, Kelly JM. Trypanosoma cruzi glycosomal glyceraldehyde-3-phosphate dehydrogenase does not conform to the ‘hotspot’ topogenic signal model. EMBO J 1990; 9(9): 2751-8.
[http://dx.doi.org/10.1002/j.1460-2075.1990.tb07462.x] [PMID: 2167831]
[118]
Sliwoski G, Kothiwale S, Meiler J, Lowe EW Jr. Computational methods in drug discovery. Pharmacol Rev 2013; 66(1): 334-95.
[http://dx.doi.org/10.1124/pr.112.007336] [PMID: 24381236]
[119]
Kapetanovic IM. Computer-aided drug discovery and development (CADDD): in silico-chemico-biological approach. Chem Biol Interact 2008; 171(2): 165-76.
[http://dx.doi.org/10.1016/j.cbi.2006.12.006] [PMID: 17229415]
[120]
Baig MH, Ahmad K, Roy S, et al. Computer aided drug design: success and limitations. Curr Pharm Des 2016; 22(5): 572-81.
[http://dx.doi.org/10.2174/1381612822666151125000550] [PMID: 26601966]
[121]
Talele TT, Khedkar SA, Rigby AC. Successful applications of computer aided drug discovery: moving drugs from concept to the clinic. Curr Top Med Chem 2010; 10(1): 127-41.
[http://dx.doi.org/10.2174/156802610790232251] [PMID: 19929824]
[122]
Lionta E, Spyrou G, Vassilatis DK, Cournia Z. Structure-based virtual screening for drug discovery: principles, applications and recent advances. Curr Top Med Chem 2014; 14(16): 1923-38.
[http://dx.doi.org/10.2174/1568026614666140929124445] [PMID: 25262799]
[123]
Macalino SJ, Gosu V, Hong S, Choi S. Role of computer-aided drug design in modern drug discovery. Arch Pharm Res 2015; 38(9): 1686-701.
[http://dx.doi.org/10.1007/s12272-015-0640-5] [PMID: 26208641]
[124]
Erlanson DA. Introduction to fragment-based drug discovery. Top Curr Chem 2012; 317: 1-32.
[PMID: 21695633]
[125]
Tanaka D. [Fragment-based drug discovery: concept and aim]. Yakugaku Zasshi 2010; 130(3): 315-23.
[http://dx.doi.org/10.1248/yakushi.130.315] [PMID: 20190516]
[126]
Bak A, Kozik V, Smolinskic A, Jampilekd J. Multidimensional (3D/4D-QSAR) probability-guided pharmacophore mapping: investigation of activity profile for a series of drug absorption promoters. RSC Advances 2016; 6(80): 76183-205.
[http://dx.doi.org/10.1039/C6RA15820J]
[127]
Devillers J. Methods for building QSARs. Methods Mol Biol 2013; 930: 3-27.
[http://dx.doi.org/10.1007/978-1-62703-059-5_1] [PMID: 23086835]
[128]
Lavecchia A, Di Giovanni C. Virtual screening strategies in drug discovery: a critical review. Curr Med Chem 2013; 20(23): 2839-60.
[http://dx.doi.org/10.2174/09298673113209990001] [PMID: 23651302]
[129]
McGaughey GB, Sheridan RP, Bayly CI, et al. Comparison of topological, shape, and docking methods in virtual screening. J Chem Inf Model 2007; 47(4): 1504-19.
[http://dx.doi.org/10.1021/ci700052x] [PMID: 17591764]
[130]
Hart TN, Read RJ. A multiple-start Monte Carlo docking method. Proteins 1992; 13(3): 206-22.
[http://dx.doi.org/10.1002/prot.340130304] [PMID: 1603810]
[131]
Irwin JJ, Shoichet BK. Docking screens for novel ligands conferring new biology. J Med Chem 2016; 59(9): 4103-20.
[http://dx.doi.org/10.1021/acs.jmedchem.5b02008] [PMID: 26913380]
[132]
Kitchen DB, Decornez H, Furr JR, Bajorath J. Docking and scoring in virtual screening for drug discovery: methods and applications. Nat Rev Drug Discov 2004; 3(11): 935-49.
[http://dx.doi.org/10.1038/nrd1549] [PMID: 15520816]
[133]
Li J, Fu A, Zhang L. An overview of scoring functions used for protein-ligand interactions in molecular docking. Interdiscip Sci 2019; 11(2): 320-8.
[http://dx.doi.org/10.1007/s12539-019-00327-w] [PMID: 30877639]
[134]
Release S. 2018-1: Schrödinger suite 2018-1 protein preparation wizard. Epik, Schrödinger, LLC, New York 2018.
[135]
Myrianthopoulos V, Lambrinidis G, Mikros E. In silico screening of compound libraries using a consensus of orthogonal methodologies. Methods Mol Biol 2018; 1824: 261-77.
[http://dx.doi.org/10.1007/978-1-4939-8630-9_15] [PMID: 30039412]
[136]
Schrödinger Release. 2018-1: LigPrep. Schrödinger, LLC, New York, NY 2018.
[137]
Schrödinger Release. 2018-1: Glide. Schrödinger, LLC, New York, NY 2018.
[138]
Friesner RA, Banks JL, Murphy RB, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem 2004; 47(7): 1739-49.
[http://dx.doi.org/10.1021/jm0306430] [PMID: 15027865]
[139]
Friesner RA, Murphy RB, Repasky MP, et al. Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J Med Chem 2006; 49(21): 6177-96.
[http://dx.doi.org/10.1021/jm051256o] [PMID: 17034125]
[140]
Hansch C, Fujita T. p-σ-π Analysis. A method for the correlation of biological activity and chemical structure. J Am Chem Soc 1964; 86(8): 1616-26.
[http://dx.doi.org/10.1021/ja01062a035]
[141]
Cherkasov A, Muratov EN, Fourches D, et al. QSAR modeling: where have you been? Where are you going to? J Med Chem 2014; 57(12): 4977-5010.
[http://dx.doi.org/10.1021/jm4004285] [PMID: 24351051]
[142]
Lill MA. Multi-dimensional QSAR in drug discovery. Drug Discov Today 2007; 12(23-24): 1013-7.
[http://dx.doi.org/10.1016/j.drudis.2007.08.004] [PMID: 18061879]
[143]
Golbraikh A, Wang XS, Zhu H, Tropsha A. Predictive QSAR modeling: methods and applications in drug discovery and chemical risk assessment Handbook of computational chemistry. Cham: Springer 2017; pp. 2303-40.
[http://dx.doi.org/10.1007/978-3-319-27282-5_37]
[144]
Peter SC, Dhanjal JK, Malik V, Radhakrishnan N, Jayakanthan M, Sundar D. Quantitative structure-activity relationship (QSAR): modeling approaches to biological applications. Encycl Bioinforma Comput Biol 2019; 2: 661-76.
[http://dx.doi.org/10.1016/B978-0-12-809633-8.20197-0]
[145]
Roy K, Kar S. SAR and QSAR in drug discovery and chemical design-some examples. In: Understanding the Basics of QSAR for Applications in Pharmaceutical Sciences and Risk Assessment. 2015; pp. 427-53.
[146]
Schrödinger Release. 2018-1: Canvas. Schrödinger, LLC, New York, NY 2018.
[147]
Sastry M, Lowrie JF, Dixon SL, Sherman W. Large-scale systematic analysis of 2D fingerprint methods and parameters to improve virtual screening enrichments. J Chem Inf Model 2010; 50(5): 771-84.
[http://dx.doi.org/10.1021/ci100062n]
[148]
Faulkner D, McKervey MA. The π-route to substituted adamantanes. Part I. J Chem Soc C 1970; 0(0): 3906-10.
[http://dx.doi.org/10.1039/J39710003906]
[149]
Geluk HW, Schlatmann JLMA. Hydride transfer reactions of the adamantyl cation (IV): Synthesis of 1,4- and 2,6-substituted adamantanes by oxidation with sulfuric acid. Rec Trav Chim 1971; 88(13): 516-20.
[http://dx.doi.org/10.1002/recl.19710900507]
[150]
Hrdina R. Directed C-H functionalization of the adamantane framework. Synthesis 2019; 51(03): 629-42.
[http://dx.doi.org/10.1055/s-0037-1610321]
[151]
Majerski Z, Hameršak Z. Rearrangement of bridgehead alcohols to polycyclic ketones by fragmentation-cyclization: 4-protoadaman-tanone (tricycle-[4.3.1.03,8]decan-4-one). Org Synth 1988; 50: 958-62.
[152]
Kolocouris N, Zoidis G, Fytas C. Facile synthetic routes to 2-oxo-1-adamantanalkanoic acids. Synlett 2007; 7(7): 1063-6.
[http://dx.doi.org/10.1055/s-2007-973899]
[153]
Chyi Tseng C, Handa I, Abdel-Sayed AN, Bauer L. N-[(aryl substitute adamantane)alkyl] 2-mercaptoacetamidines, their corresponding disulfides and 5-phosphorothioates. Tetrahedron 1988; 44(7): 1893-904.
[http://dx.doi.org/10.1016/S0040-4020(01)90332-1]
[154]
Endo Y, Sawabe T, Taoda Y. Electronic effects of icosahedral carboranes. Retentive solvolysis of (1,2-Dicarba-closo-dodecaboran-1-yl)benzyl p-Toluenesulfonates. J Am Chem Soc 2000; 122(1): 180-1.
[http://dx.doi.org/10.1021/ja993517n]
[155]
Natarajan A, Joy A, Kaanumalle LS, Scheffer JR, Ramamurthy V. Enhanced enantio- and diastereoselectivity via confinement and cation binding: yang photocyclization of 2-benzoyladamantane derivatives within zeolites. J Org Chem 2002; 67(24): 8339-50.
[http://dx.doi.org/10.1021/jo0260793] [PMID: 12444610]
[156]
Papanastasiou I, Tsotinis A, Kolocouris N, Nikas SP, Vamvakides A. New aminoadamantane derivatives with antiproliferative activity. Med Chem Res 2014; 23(4): 1966-75.
[http://dx.doi.org/10.1007/s00044-013-0798-7]
[157]
Volkov OA, Kinch L, Ariagno C, et al. Relief of autoinhibition by conformational switch explains enzyme activation by a catalytically dead paralog. eLife 2016; 5 e20198
[http://dx.doi.org/10.7554/eLife.20198] [PMID: 27977001]
[158]
Schönherr H, Cernak T. Profound methyl effects in drug discovery and a call for new C-H methylation reactions. Angew Chem Int Ed Engl 2013; 52(47): 12256-67.
[http://dx.doi.org/10.1002/anie.201303207] [PMID: 24151256]
[159]
Klebe G. Applying thermodynamic profiling in lead finding and optimization. Nat Rev Drug Discov 2015; 14(2): 95-110.
[http://dx.doi.org/10.1038/nrd4486] [PMID: 25614222]
[160]
Dunitz JD. Win some, lose some: enthalpy-entropy compensation in weak intermolecular interactions. Chem Biol 1995; 2(11): 709-12.
[http://dx.doi.org/10.1016/1074-5521(95)90097-7] [PMID: 9383477]
[161]
Lumry R, Rajender S. Enthalpy-entropy compensation phenomena in water solutions of proteins and small molecules: a ubiquitous property of water. Biopolymers 1970; 9(10): 1125-227.
[http://dx.doi.org/10.1002/bip.1970.360091002] [PMID: 4918636]
[162]
Wienen-Schmidt B, Jonker HRA, Wulsdorf T, et al. Paradoxically, most flexible ligand binds most entropy-favored: intriguing impact of ligand flexibility and solvation on drug-kinase binding. J Med Chem 2018; 61(14): 5922-33.
[http://dx.doi.org/10.1021/acs.jmedchem.8b00105] [PMID: 29909615]
[163]
Motiejunas D, Wade RC. Structural, energetic, and dynamic aspects of ligand–receptor interactions Comprehensive medicinal chemistry II. Oxford: Elsevier 2007; pp. 193-213.
[http://dx.doi.org/10.1016/B0-08-045044-X/00250-9]
[164]
Spyrakis F, Ahmed MH, Bayden AS, Cozzini P, Mozzarelli A, Kellogg GE. The roles of water in the protein matrix: a largely untapped resource for drug discovery. J Med Chem 2017; 60(16): 6781-827.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00057] [PMID: 28475332]
[165]
SZMAP. OpenEye Scientific Software Inc. Santa Fe, NM, USA 2015.
[166]
Bayden AS, Moustakas DT, Joseph-McCarthy D, Lamb ML. Evaluating free energies of binding and conservation of crystallographic waters using SZMAP. J Chem Inf Model 2015; 55(8): 1552-65.
[http://dx.doi.org/10.1021/ci500746d] [PMID: 26176600]
[167]
Myrianthopoulos V, Gaboriaud-Kolar N, Tallant C, et al. Discovery and optimization of a selective ligand for the switch/sucrose nonfermenting-related bromodomains of polybromo protein-1 by the use of virtual screening and hydration analysis. J Med Chem 2016; 59(19): 8787-803.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00355] [PMID: 27617704]
[168]
Todeschini R, Consonni V. Handbook of molecular descriptors methods and principles in medicinal chemistry. WILEY-VCH Verlag GmbH. 2000.
[http://dx.doi.org/10.1002/9783527613106]

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