Unveiling the Targets Involved in the Quest of Antileishmanial Leads Using In silico Methods

Author(s): Pone K. Boniface*, Cinthya M. Sano, Ferreira I. Elizabeth

Journal Name: Current Drug Targets

Volume 21 , Issue 7 , 2020


  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Leishmaniasis is a neglected tropical disease associated with several clinical manifestations, including cutaneous, mucocutaneous, and visceral forms. As currently available drugs have some limitations (toxicity, resistance, among others), the target-based identification has been an important approach to develop new leads against leishmaniasis. The present study aims to identify targets involved in the pharmacological action of potent antileishmanial compounds.

Methods: The literature information regarding molecular interactions of antileishmanial compounds studied over the past half-decade is discussed. The information was obtained from databases such as Wiley, SciFinder, Science Direct, National Library of Medicine, American Chemical Society, Scientific Electronic Library Online, Scopus, Springer, Google Scholar, Web of Science, etc.

Results: Numerous in vitro antileishmanial compounds showed affinity and selective interactions with enzymes such as arginase, pteridine reductase 1, trypanothione reductase, pyruvate kinase, among others, which are crucial for the survival and virulence of the Leishmania parasite.

Conclusion: The in-silico activity of small molecules (enzymes, proteins, among others) might be used as pharmacological tools to develop candidate compounds for the treatment of leishmaniasis. As some pharmacologically active compounds may act on more than one target, additional studies of the mechanism (s) of action of potent antileishmanial compounds might help to better understand their pharmacological action. Also, the optimization of promising antileishmanial compounds might improve their biological activity.

Keywords: Leishmaniasis, bioinformatics, in silico, pharmacology, drug targets, molecular modelling.

[1]
World Health Organization (WHO). 2019 The leishmaniases The fact sheets, 2019 https://www.who.int/news-room/fact-sheets/ detail/leishmaniasis accessed on 04th July 2019.
[2]
Moore EM, Lockwood DN. Treatment of visceral leishmaniasis. J Glob Infect Dis 2010; 2(2): 151-8.
[http://dx.doi.org/10.4103/0974-777X.62883] [PMID: 20606971]
[3]
Singh N, Kumar M, Singh RK. Leishmaniasis: current status of available drugs and new potential drug targets. Asian Pac J Trop Med 2012; 5(6): 485-97.
[http://dx.doi.org/10.1016/S1995-7645(12)60084-4] [PMID: 22575984]
[4]
Gupta G, Oghumu S, Satoskar AR. Mechanisms of immune evasion in leishmaniasis. Adv Appl Microbiol 2013; 82: 155-84.
[http://dx.doi.org/10.1016/B978-0-12-407679-2.00005-3] [PMID: 23415155]
[5]
Borsari C, Quotadamo A, Ferrari S, et al. Scaffolds and biological targets avenue to fight against drug resistance in leishmaniasis. Adv Protein Chem Str 2018; 113: 119-42.
[http://dx.doi.org/10.1016/bs.armc.2018.08.002]
[6]
Yu W, MacKerell AD Jr. Jr. Computer-aided drug design methods. Methods Mol Biol 2017; 1520: 85-106.
[http://dx.doi.org/10.1007/978-1-4939-6634-9_5] [PMID: 27873247]
[7]
Govindaraj RG, Brylinski M. Comparative assessment of strategies to identify similar ligand-binding pockets in proteins. BMC Bioinformatics 2018; 19(1): 91.
[http://dx.doi.org/10.1186/s12859-018-2109-2] [PMID: 29523085]
[8]
Kastritis PL, Bonvin AM. On the binding affinity of macromolecular interactions: daring to ask why proteins interact. J R Soc Interface 2012; 10(79)20120835
[http://dx.doi.org/10.1098/rsif.2012.0835] [PMID: 23235262]
[9]
Souza-Silva F, Bourguignon SC, Pereira BA, et al. Epoxy-α-lapachone has in vitro and in vivo anti-leishmania (Leishmania) amazonensis effects and inhibits serine proteinase activity in this parasite. Antimicrob Agents Chemother 2015; 59(4): 1910-8.
[http://dx.doi.org/10.1128/AAC.04742-14] [PMID: 25583728]
[10]
Taha M, Ismail NH, Ali M, et al. Molecular hybridization conceded exceptionally potent quinolinyl-oxadiazole hybrids through phenyl linked thiosemicarbazide antileishmanial scaffolds: In silico validation and SAR studies. Bioorg Chem 2017 a; 71: 192-200.
[http://dx.doi.org/10.1016/j.bioorg.2017.02.005] [PMID: 28228228]
[11]
Rauf MK, Shaheen U, Asghar F, et al. Antileishmanial, DNA interaction, and docking studies of some ferrocene-based heteroleptic pentavalent antimonials. Arch Pharm (Weinheim) 2016; 349(1): 50-62.
[http://dx.doi.org/10.1002/ardp.201500312] [PMID: 26627058]
[12]
Chávez-Fumagalli MA, Lage DP, Tavares GSV, et al. In silico Leishmania proteome mining applied to identify drug target potential to be used to treat against visceral and tegumentary leishmaniasis. J Mol Graph Model 2019; 87: 89-97.
[http://dx.doi.org/10.1016/j.jmgm.2018.11.014] [PMID: 30522092]
[13]
Taslimi Y, Zahedifard F, Rafati S. Leishmaniasis and various immunotherapeutic approaches. Parasitology 2018; 145(4): 497-507.
[http://dx.doi.org/10.1017/S003118201600216X] [PMID: 27974063]
[14]
Sundar S, Chakravarty J. An update on pharmacotherapy for leishmaniasis. Expert Opin Pharmacother 2015; 16(2): 237-52.
[http://dx.doi.org/10.1517/14656566.2015.973850] [PMID: 25346016]
[15]
Muhammad MT, Ghouri N, Khan KM, Arshia , Choudhary MI. Perveen S. Arshia, Choudhary, M.I.; Perveen, S. Synthesis of thiocarbohydrazones and evaluation of their in vitro antileishmanial activity. Med Chem 2018; 14(7): 725-32.
[http://dx.doi.org/10.2174/1573406414666180115094630] [PMID: 29332596]
[16]
Bailey MS, Lockwood DN. Cutaneous leishmaniasis. Clin Dermatol 2007; 25(2): 203-11.
[http://dx.doi.org/10.1016/j.clindermatol.2006.05.008] [PMID: 17350500]
[17]
Martins AL, Barreto JA, Lauris JR, Martins AC. American tegumentary leishmaniasis: correlations among immunological, histopathological and clinical parameters. An Bras Dermatol 2014; 89(1): 52-8.
[http://dx.doi.org/10.1590/abd1806-4841.20142226] [PMID: 24626648]
[18]
de Vries HJ, Reedijk SH, Schallig HD. Cutaneous leishmaniasis: recent developments in diagnosis and management. Am J Clin Dermatol 2015; 16(2): 99-109.
[http://dx.doi.org/10.1007/s40257-015-0114-z] [PMID: 25687688]
[19]
Aronson N, Herwaldt BL, Libman M, et al. diagnosis and treatment of leishmaniasis: clinical practice guidelines by the infectious diseases society of america (idsa) and the American Society of Tropical Medicine and Hygiene (ASTMH). Am J Trop Med Hyg 2017; 96(1): 24-45.
[http://dx.doi.org/10.4269/ajtmh.16-84256] [PMID: 27927991]
[20]
Alvar J, Vélez ID, Bern C, et al. WHO Leishmaniasis Control Team. Leishmaniasis worldwide and global estimates of its incidence. PLoS One 2012; 7(5) e35671
[http://dx.doi.org/10.1371/journal.pone.0035671] [PMID: 22693548]
[21]
World Health Organization (WHO) Leishmaniasis. Epidemiological situation, 2017,. https://www.who.int/leishmaniasis/burden/ en/Accessed on 4th September 2019
[22]
Bilgic-Temel A, Murrell DF, Uzun S. Cutaneous leishmaniasis: A neglected disfiguring disease for women. Int J Womens Dermatol 2019; 5(3): 158-65.
[http://dx.doi.org/10.1016/j.ijwd.2019.01.002] [PMID: 31360749]
[23]
Yanik M, Gurel MS, Simsek Z, Kati M. The psychological impact of cutaneous leishmaniasis. Clin Exp Dermatol 2004; 29(5): 464-7.
[http://dx.doi.org/10.1111/j.1365-2230.2004.01605.x] [PMID: 15347324]
[24]
Kassi M, Kassi M, Afghan AK, Rehman R, Kasi PM. Marring leishmaniasis: the stigmatization and the impact of cutaneous leishmaniasis in Pakistan and Afghanistan. PLoS Negl Trop Dis 2008; 2(10)e259
[http://dx.doi.org/10.1371/journal.pntd.0000259] [PMID: 18958168]
[25]
Vares B, Mohseni M, Heshmatkhah A, et al. Quality of life in patients with cutaneous leishmaniasis. Arch Iran Med 2013; 16(8): 474-7.
[PMID: 23906253]
[26]
Miranda Lessa M, Andrade Lessa H, Castro TWN, et al. Mucosal leishmaniasis: epidemiological and clinical aspects. Rev Bras Otorrinolaringol (Engl Ed) 2007; 73(6): 843-7.
[http://dx.doi.org/10.1016/S1808-8694(15)31181-2] [PMID: 18278231]
[27]
Queiroz MJ, Alves JG, Correia JB. [Visceral leishmaniasis: clinical and epidemiological features of children in an endemic area]. J Pediatr (Rio J) 2004; 80(2): 141-6.
[http://dx.doi.org/10.2223/1154] [PMID: 15079185]
[28]
Maroli M, Feliciangeli MD, Bichaud L, Charrel RN, Gradoni L. Phlebotomine sandflies and the spreading of leishmaniases and other diseases of public health concern. Med Vet Entomol 2013; 27(2): 123-47.
[http://dx.doi.org/10.1111/j.1365-2915.2012.01034.x] [PMID: 22924419]
[29]
Ready PD. Biology of phlebotomine sand flies as vectors of disease agents. Annu Rev Entomol 2013; 58: 227-50.
[http://dx.doi.org/10.1146/annurev-ento-120811-153557] [PMID: 23317043]
[30]
Kumar A. Leishmania and leishmaniasis. New York: Springer 2013; pp. 7-10.
[http://dx.doi.org/10.1007/978-1-4614-8869-9]
[31]
Alves MJ, Ulisses C, Lima CGM, Dilermando AFJ, Carina M. Visceral leishmaniasis: situation diagnosis from the perspective of disease control in Brazil. J Microbiol Exp 2018; 6(2): 104-6.
[32]
Uzun S, Gürel MS, Durdu M, et al. Clinical practice guidelines for the diagnosis and treatment of cutaneous leishmaniasis in Turkey. Int J Dermatol 2018; 57(8): 973-82.
[http://dx.doi.org/10.1111/ijd.14002] [PMID: 29663351]
[33]
Sundar S, Singh OP. Molecular diagnosis of visceral leishmaniasis. Mol Diagn Ther 2018; 22(4): 443-57.
[http://dx.doi.org/10.1007/s40291-018-0343-y] [PMID: 29922885]
[34]
Salam N, Al-Shaqha WM, Azzi A. Leishmaniasis in the middle East: incidence and epidemiology. PLoS Negl Trop Dis 2014; 8(10)e3208
[http://dx.doi.org/10.1371/journal.pntd.0003208] [PMID: 25275483]
[35]
Silva BV, Silva BNM. Thio- and semicarbazones: Hope in the search for treatment of leishmaniasis and Chagas disease. Med Chem 2017; 13(2): 110-26.
[http://dx.doi.org/10.2174/1573406412666160909152614] [PMID: 27629824]
[36]
Claborn DM. The biology and control of leishmaniasis vectors. J Glob Infect Dis 2010; 2(2): 127-34.
[http://dx.doi.org/10.4103/0974-777X.62866] [PMID: 20606968]
[37]
Davies CR, Kaye P, Croft SL, Sundar S. Leishmaniasis: new approaches to disease control. BMJ 2003; 326(7385): 377-82.
[http://dx.doi.org/10.1136/bmj.326.7385.377] [PMID: 12586674]
[38]
Hosen MI, Tanmoy AM, Mahbuba DA, et al. Application of a subtractive genomics approach for in silico identification and characterization of novel drug targets in Mycobacterium tuberculosis F11. Interdiscip Sci 2014; 6(1): 48-56.
[http://dx.doi.org/10.1007/s12539-014-0188-y] [PMID: 24464704]
[39]
Vijayakumar S, Das P. Recent progress in drug targets and inhibitors towards combating leishmaniasis. Acta Trop 2018; 181: 95-104.
[http://dx.doi.org/10.1016/j.actatropica.2018.02.010] [PMID: 29452111]
[40]
Croston GE. The utility of target-based discovery. Expert Opin Drug Discov 2017; 12(5): 427-9.
[http://dx.doi.org/10.1080/17460441.2017.1308351] [PMID: 28306350]
[41]
Birsoy K, Wang T, Chen WW, Freinkman E, Abu-Remaileh M, Sabatini DM. An essential role of the mitochondrial electron transport chain in cell proliferation is to enable aspartate synthesis. Cell 2015; 162(3): 540-51.
[http://dx.doi.org/10.1016/j.cell.2015.07.016] [PMID: 26232224]
[42]
Zhao RZ, Jiang S, Zhang L, Yu ZB. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int J Mol Med 2019; 44(1): 3-15.
[http://dx.doi.org/10.3892/ijmm.2019.4188] [PMID: 31115493]
[43]
Sevrioukova IF, Poulos TL. Understanding the mechanism of cytochrome P450 3A4: recent advances and remaining problems. Dalton Trans 2013; 42(9): 3116-26.
[http://dx.doi.org/10.1039/C2DT31833D] [PMID: 23018626]
[44]
Verma S, Mehta A, Shaha C. CYP5122A1, a novel cytochrome P450 is essential for survival of Leishmania donovani. PLoS One 2011; 6(9)e25273
[http://dx.doi.org/10.1371/journal.pone.0025273] [PMID: 21966477]
[45]
Mondal S, Roy JJ, Bera T. Generation of adenosine tri-phosphate in Leishmania donovani amastigote forms. Acta Parasitol 2014; 59(1): 11-6.
[http://dx.doi.org/10.2478/s11686-014-0203-9] [PMID: 24570045]
[46]
Menna-Barreto RF, de Castro SL. The double-edged sword in pathogenic trypanosomatids: the pivotal role of mitochondria in oxidative stress and bioenergetics. BioMed Res Int 2014; 2014614014
[http://dx.doi.org/10.1155/2014/614014] [PMID: 24800243]
[47]
Murphy MP. How mitochondria produce reactive oxygen species. Biochem J 2009; 417(1): 1-13.
[http://dx.doi.org/10.1042/BJ20081386] [PMID: 19061483]
[48]
Van Hellemond JJ, Tielens AG. Inhibition of the respiratory chain results in a reversible metabolic arrest in Leishmania promastigotes. Mol Biochem Parasitol 1997; 85(1): 135-8.
[http://dx.doi.org/10.1016/S0166-6851(97)02828-4] [PMID: 9108556]
[49]
Dey R, Meneses C, Salotra P, Kamhawi S, Nakhasi HL, Duncan R. Characterization of a Leishmania stage-specific mitochondrial membrane protein that enhances the activity of cytochrome c oxidase and its role in virulence. Mol Microbiol 2010; 77(2): 399-414.
[http://dx.doi.org/10.1111/j.1365-2958.2010.07214.x] [PMID: 20497506]
[50]
da Trindade Granato J, Dos Santos JA, Calixto SL, et al. Novel steroid derivatives: synthesis, antileishmanial activity, mechanism of action, and in silico physicochemical and pharmacokinetics studies. Biomed Pharmacother 2018; 106: 1082-90.
[http://dx.doi.org/10.1016/j.biopha.2018.07.056] [PMID: 30119174]
[51]
Lima SCM, Pacheco JDS, Marques AM, et al. Leishmanicidal activity of withanolides from Aurelianafasciculata var. Fasciculata. Molecules 2018; 23(12)e3160
[http://dx.doi.org/10.3390/molecules23123160] [PMID: 30513673]
[52]
Melo TS, Gattass CR, Soares DC, et al. Oleanolic acid (OA) as an antileishmanial agent: Biological evaluation and in silico mechanistic insights. Parasitol Int 2016; 65(3): 227-37.
[http://dx.doi.org/10.1016/j.parint.2016.01.001] [PMID: 26772973]
[53]
Stevanović S, Perdih A, Senćanski M, et al. In silico discovery of a substituted 6-methoxy-quinalidine with leishmanicidal activity in Leishmania infantum. Molecules 2018; 23(4)e772
[http://dx.doi.org/10.3390/molecules23040772] [PMID: 29584709]
[54]
Pandey SC, Jha A, Kumar A, Samant M. Evaluation of antileishmanial potential of computationally screened compounds targeting DEAD-box RNA helicase of Leishmania donovani. Int J Biol Macromol 2019; 121: 480-7.
[http://dx.doi.org/10.1016/j.ijbiomac.2018.10.053] [PMID: 30321635]
[55]
Reguera RM, Balaña-Fouce R, Showalter M, Hickerson S, Beverley SM. Leishmania major lacking arginase (ARG) are auxotrophic for polyamines but retain infectivity to susceptible BALB/c mice. Mol Biochem Parasitol 2009; 165(1): 48-56.
[http://dx.doi.org/10.1016/j.molbiopara.2009.01.001] [PMID: 19393161]
[56]
da Silva ER, Maquiaveli CdoC, Magalhães PP. The leishmanicidal flavonols quercetin and quercitrin target Leishmania (Leishmania) amazonensis arginase. Exp Parasitol 2012; 130(3): 183-8.
[http://dx.doi.org/10.1016/j.exppara.2012.01.015] [PMID: 22327179]
[57]
Balaña-Fouce R, Prada CF, Requena JM, et al. Indotecan (LMP400) and AM13-55: two novel indenoisoquinolines show potential for treating visceral leishmaniasis. Antimicrob Agents Chemother 2012; 56(10): 5264-70.
[http://dx.doi.org/10.1128/AAC.00499-12] [PMID: 22850521]
[58]
Nieto-Meneses R, Castillo R, Hernández-Campos A, et al. In vitro activity of new N-benzyl-1H-benzimidazol-2-amine derivatives against cutaneous, mucocutaneous and visceral Leishmania species. Exp Parasitol 2018; 184: 82-9.
[http://dx.doi.org/10.1016/j.exppara.2017.11.009] [PMID: 29191699]
[59]
Fairlamb AH, Blackburn P, Ulrich P, Chait BT, Cerami A. Trypanothione: a novel bis(glutathionyl)spermidine cofactor for glutathione reductase in trypanosomatids. Science 1985; 227(4693): 1485-7.
[http://dx.doi.org/10.1126/science.3883489] [PMID: 3883489]
[60]
Koch O, Cappel D, Nocker M, et al. Molecular dynamics reveal binding mode of glutathionylspermidine by trypanothione synthetase. PLoS One 2013; 8(2)e56788
[http://dx.doi.org/10.1371/journal.pone.0056788] [PMID: 23451087]
[61]
Ilari A, Fiorillo A, Genovese I, Colotti G. Polyamine-trypanothione pathway: an update. Future Med Chem 2017; 9(1): 61-77.
[http://dx.doi.org/10.4155/fmc-2016-0180] [PMID: 27957878]
[62]
Turcano L, Torrente E, Missineo A, et al. Identification and binding mode of a novel Leishmania Trypanothione reductase inhibitor from high throughput screening. PLoS Negl Trop Dis 2018; 12(11)e0006969
[http://dx.doi.org/10.1371/journal.pntd.0006969] [PMID: 30475811]
[63]
Jacomini AP, Silva MJV, Silva RGM, et al. Synthesis and evaluation against Leishmania amazonensis of novel pyrazolo[3,4-d]pyridazinone-N-acylhydrazone-(bi)thiophene hybrids. Eur J Med Chem 2016; 124: 340-9.
[http://dx.doi.org/10.1016/j.ejmech.2016.08.048] [PMID: 27597410]
[64]
Cavazzuti A, Paglietti G, Hunter WN, et al. Discovery of potent pteridine reductase inhibitors to guide antiparasite drug development. Proc Natl Acad Sci USA 2008; 105(5): 1448-53.
[http://dx.doi.org/10.1073/pnas.0704384105] [PMID: 18245389]
[65]
Corona P, Gibellini F, Cavalli A, et al. Structure-based selectivity optimization of piperidine-pteridine derivatives as potent Leishmania pteridine reductase inhibitors. J Med Chem 2012; 55(19): 8318-29.
[http://dx.doi.org/10.1021/jm300563f] [PMID: 22946585]
[66]
Schüttelkopf AW, Hardy LW, Beverley SM, Hunter WN. Structures of Leishmania major pteridine reductase complexes reveal the active site features important for ligand binding and to guide inhibitor design. J Mol Biol 2005; 352(1): 105-16.
[http://dx.doi.org/10.1016/j.jmb.2005.06.076] [PMID: 16055151]
[67]
Taha M, Ismail NH, Imran S, et al. Synthesis and molecular modelling studies of phenyl linked oxadiazole-phenylhydrazone hybrids as potent antileishmanial agents. Eur J Med Chem 2017 b; 126: 1021-33.
[http://dx.doi.org/10.1016/j.ejmech.2016.12.019] [PMID: 28012342]
[68]
Rashid U, Sultana R, Shaheen N, et al. Structure based medicinal chemistry-driven strategy to design substituted dihydropyrimidines as potential antileishmanial agents. Eur J Med Chem 2016; 115: 230-44.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.022] [PMID: 27017551]
[69]
Bekhit AA, Hassan AM, Abd El Razik HA, El-Miligy MM, El-Agroudy EJ. Bekhit, Ael.-D. New heterocyclic hybrids of pyrazole and its bioisosteres: design, synthesis and biological evaluation as dual antimalarial-antileishmanial agents. Eur J Med Chem 2015; 94: 30-44.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.038] [PMID: 25768697]
[70]
Khademvatan S, Eskandari K, Hazrati-Tappeh K, et al. In silico and in vitro comparative activity of green tea components against Leishmania infantum. J Glob Antimicrob Resist 2019; 18: 187-94.
[http://dx.doi.org/10.1016/j.jgar.2019.02.008] [PMID: 30797085]
[71]
Patil SR, Bollikonda S, Patil RH, et al. Microwave-assisted synthesis of novel 5-substituted benzylidene amino-2-butyl benzofuran-3-yl-4-methoxyphenyl methanones as antileishmanial and antioxidant agents. Bioorg Med Chem Lett 2018; 28(3): 482-7.
[http://dx.doi.org/10.1016/j.bmcl.2017.12.013] [PMID: 29258770]
[72]
Patil SR, Asrondkar A, Patil V, et al. Antileishmanial potential of fused 5-(pyrazin-2-yl)-4H-1,2,4-triazole-3-thiols: Synthesis, biological evaluations and computational studies. Bioorg Med Chem Lett 2017; 27(16): 3845-50.
[http://dx.doi.org/10.1016/j.bmcl.2017.06.053] [PMID: 28693910]
[73]
Sangshetti JN, Kalam Khan FA, Kulkarni AA, et al. Antileishmanial activity of novel indolyl-coumarin hybrids: Design, synthesis, biological evaluation, molecular docking study and in silico ADME prediction. Bioorg Med Chem Lett 2016; 26(3): 829-35.
[http://dx.doi.org/10.1016/j.bmcl.2015.12.085] [PMID: 26778149]
[74]
Pandey RK, Kumbhar BV, Sundar S, Kunwar A, Prajapati VK. Structure-based virtual screening, molecular docking, ADMET and molecular simulations to develop benzoxaborole analogs as potential inhibitor against Leishmania donovani trypanothione reductase. J Recept Signal Transduct Res 2017 a; 37(1): 60-70.
[http://dx.doi.org/10.3109/10799893.2016.1171344] [PMID: 27147242]
[75]
Pandey RK, Verma P, Sharma D, Bhatt TK, Sundar S, Prajapati VK. High-throughput virtual screening and quantum mechanics approach to develop imipramine analogues as leads against trypanothione reductase of leishmania. Biomed Pharmacother 2016 b; 83: 141-52.
[http://dx.doi.org/10.1016/j.biopha.2016.06.010] [PMID: 27470561]
[76]
da Silva AD, Dos Santos JA, Machado PA, et al. Insights about resveratrol analogs against trypanothione reductase of Leishmania braziliensis: Molecular modeling, computational docking and in vitro antileishmanial studies. J Biomol Struct Dyn 2019; 37(11): 2960-9.
[http://dx.doi.org/10.1080/07391102.2018.1502096] [PMID: 30058445]
[77]
Ortalli M, Ilari A, Colotti G, et al. Identification of chalcone-based antileishmanial agents targeting trypanothione reductase. Eur J Med Chem 2018; 152: 527-41.
[http://dx.doi.org/10.1016/j.ejmech.2018.04.057] [PMID: 29758517]
[78]
Ramu D, Garg S, Ayana R, et al. Novel β-carboline-quinazolinone hybrids disrupt Leishmania donovani redox homeostasis and show promising antileishmanial activity. Biochem Pharmacol 2017; 129: 26-42.
[http://dx.doi.org/10.1016/j.bcp.2016.12.012] [PMID: 28017772]
[79]
Pandey RK, Kumbhar BV, Srivastava S, et al. Febrifugine analogues as Leishmania donovani trypanothione reductase inhibitors: binding energy analysis assisted by molecular docking, ADMET and molecular dynamics simulation. J Biomol Struct Dyn 2017; 35(1): 141-58.
[http://dx.doi.org/10.1080/07391102.2015.1135298] [PMID: 27043972]
[80]
Iman M, Kaboutaraki HB, Jafari R, et al. Molecular dynamics simulation and docking studies of selenocyanate derivatives as antileishmanial agents. Comb Chem High Throughput Screen 2016; 19(10): 847-54.
[http://dx.doi.org/10.2174/1386207319666160907102235] [PMID: 27604957]
[81]
Verma S, Dixit R, Pandey KC. Cysteine proteases: Modes of activation and future prospects as pharmacological targets. Front Pharmacol 2016; 7: 107.
[http://dx.doi.org/10.3389/fphar.2016.00107] [PMID: 27199750]
[82]
De Luca L, Ferro S, Buemi MR, et al. Discovery of benzimidazole-based Leishmania mexicana cysteine protease CPB2.8ΔCTE inhibitors as potential therapeutics for leishmaniasis. Chem Biol Drug Des 2018; 92(3): 1585-96.
[http://dx.doi.org/10.1111/cbdd.13326] [PMID: 29729080]
[83]
Sodero AC, Dos Santos AC, Mello JF, et al. Oligopeptidase B and B2: comparative modelling and virtual screening as searching tools for new antileishmanial compounds. Parasitology 2017; 144(4): 536-45.
[http://dx.doi.org/10.1017/S0031182016002237] [PMID: 28031079]
[84]
Gomes MN, Alcântara LM, Neves BJ, et al. Computer-aided discovery of two novel chalcone-like compounds active and selective against Leishmania infantum. Bioorg Med Chem Lett 2017; 27(11): 2459-64.
[http://dx.doi.org/10.1016/j.bmcl.2017.04.010] [PMID: 28434763]
[85]
Saha S, Acharya C, Pal U, et al. A novel spirooxindole derivative inhibits the growth of Leishmania donovani parasites both in vitro and in vivo by targeting type IB topoisomerase. Antimicrob Agents Chemother 2016; 60(10): 6281-93.
[http://dx.doi.org/10.1128/AAC.00352-16] [PMID: 27503653]
[86]
Tejería A, Pérez-Pertejo Y, Reguera RM, et al. Antileishmanial activity of new hybrid tetrahydroquinoline and quinoline derivatives with phosphorus substituents. Eur J Med Chem 2019; 162: 18-31.
[http://dx.doi.org/10.1016/j.ejmech.2018.10.065] [PMID: 30408746]
[87]
Choi JY, Podust LM, Roush WR. Drug strategies targeting CYP51 in neglected tropical diseases. Chem Rev 2014; 114(22): 11242-71.
[http://dx.doi.org/10.1021/cr5003134] [PMID: 25337991]
[88]
de Souza W, Rodrigues JC. Sterol biosynthesis pathway as target for anti-trypanosomatid drugs. Interdiscip Perspect Infect Dis 2009; 2009642502
[http://dx.doi.org/10.1155/2009/642502] [PMID: 19680554]
[89]
McCall LI, El Aroussi A, Choi JY, et al. Targeting Ergosterol biosynthesis in Leishmania donovani: essentiality of sterol 14 alpha-demethylase. PLoS Negl Trop Dis 2015; 9(3)e0003588
[http://dx.doi.org/10.1371/journal.pntd.0003588] [PMID: 25768284]
[90]
Pucadyil TJ, Tewary P, Madhubala R, Chattopadhyay A. Cholesterol is required for Leishmania donovani infection: implications in leishmaniasis. Mol Biochem Parasitol 2004; 133(2): 145-52.
[http://dx.doi.org/10.1016/j.molbiopara.2003.10.002] [PMID: 14698427]
[91]
Keighobadi M, Emami S, Fakhar M, Shokri A, Mirzaei H, Hosseini Teshnizi S. Repurposing azole antifungals into antileishmanials: Novel 3-triazolylflavanones with promising in vitro antileishmanial activity against Leishmania major. Parasitol Int 2019; 69: 103-9.
[http://dx.doi.org/10.1016/j.parint.2018.12.006] [PMID: 30582997]
[92]
Ibrar A, Zaib S, Jabeen F, Iqbal J, Saeed A. Unraveling the alkaline phosphatase inhibition, anticancer, and antileishmanial potential of coumarin-triazolothiadiazine hybrids: Design, synthesis, and molecular docking analysis. Arch Pharm (Weinheim) 2016; 349(7): 553-65.
[http://dx.doi.org/10.1002/ardp.201500392] [PMID: 27214743]
[93]
Viana GM, Soares DC, Santana MV, et al. Antileishmanial thioureas: Synthesis, biological activity and in silico evaluations of new promising derivatives. Chem Pharm Bull (Tokyo) 2017; 65(10): 911-9.
[http://dx.doi.org/10.1248/cpb.c17-00293] [PMID: 28966275]
[94]
Waseem D, Butt AF, Haq IU, Bhatti MH, Khan GM. Carboxylate derivatives of tributyltin (IV) complexes as anticancer and antileishmanial agents. Daru 2017; 25(1): 8.
[http://dx.doi.org/10.1186/s40199-017-0174-0] [PMID: 28376844]
[95]
Mao W, Daligaux P, Lazar N, et al. Biochemical analysis of leishmanial and human GDP-Mannose Pyrophosphorylases and selection of inhibitors as new leads. Sci Rep 2017; 7(1): 751.
[http://dx.doi.org/10.1038/s41598-017-00848-8] [PMID: 28389670]
[96]
Daligaux P, Pomel S, Leblanc K, Loiseau PM, Cavé C. Simple and efficient synthesis of 5′-aryl-5′-deoxyguanosine analogs by azide-alkyne click reaction and their antileishmanial activities. Mol Divers 2016; 20(2): 507-19.
[http://dx.doi.org/10.1007/s11030-015-9652-9] [PMID: 26754628]
[97]
Kashif M, Tabrez S, Husein A, et al. Identification of novel inhibitors against UDP-galactopyranose mutase to combat leishmaniasis. J Cell Biochem 2018; 119(3): 2653-65.
[http://dx.doi.org/10.1002/jcb.26433] [PMID: 29058760]
[98]
Khan FA, Zaheer Z, Sangshetti JN, Patil RH, Farooqui M. Antileishmanial evaluation of clubbed bis(indolyl)-pyridine derivatives: One-pot synthesis, in vitro biological evaluations and in silico ADME prediction. Bioorg Med Chem Lett 2017; 27(3): 567-73.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.018] [PMID: 28003139]
[99]
Wyllie S, Thomas M, Patterson S, et al. Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis. Nature 2018; 560(7717): 192-7.
[http://dx.doi.org/10.1038/s41586-018-0356-z] [PMID: 30046105]
[100]
Jones LH, Bunnage ME. Applications of chemogenomic library screening in drug discovery. Nat Rev Drug Discov 2017; 16(4): 285-96.
[http://dx.doi.org/10.1038/nrd.2016.244] [PMID: 28104905]
[101]
de Lima Serafim V, Félix MB, Frade Silva DK, et al. New thiophene-acridine compounds: Synthesis, antileishmanial activity, DNA binding, chemometric, and molecular docking studies. Chem Biol Drug Des 2018; 91(6): 1141-55.
[http://dx.doi.org/10.1111/cbdd.13176] [PMID: 29415325]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 21
ISSUE: 7
Year: 2020
Published on: 17 June, 2020
Page: [681 - 712]
Pages: 32
DOI: 10.2174/1389450121666200128112948
Price: $65

Article Metrics

PDF: 13
HTML: 6
PRC: 1