Generic placeholder image

Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Research Article

Synthesis and Anticancer Activity of Thiadiazole Containing Thiourea, Benzothiazole and Imidazo[2,1-b][1,3,4]thiadiazole Scaffolds

Author(s): Stephen P. Avvaru, Malleshappa N. Noolvi*, Uttam A. More, Sudipta Chakraborty, Ashutosh Dash, Tejraj M. Aminabhavi, Kumar P. Narayan and Vishnu Sutariya

Volume 17, Issue 7, 2021

Published on: 19 May, 2020

Page: [750 - 765] Pages: 16

DOI: 10.2174/1573406416666200519085626

Price: $65

Abstract

Background: A great array of nitrogen-containing heterocyclic rings were being extensively explored for their functional versatility in the field of medicine, especially in anticancer research. 1,3,4- thiadiazole is one of such heterocyclic rings with promising anticancer activity against several cancer cell lines, inhibiting diverse biological targets.

Introduction: The 1,3,4-thiadiazole, when equipped with other heterocyclic scaffolds, has displayed enhanced anticancer properties. The thiourea, benzothiazole, imidazo[2,1,b][1,3,4]-thiadiazoles are such potential scaffolds with promising anticancer activity.

Methods: A new series of 5-substituted-1,3,4-thiadiazoles linked with phenyl thiourea, benzothiazole and 2,6-disubstituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized and tested for invitro anticancer activity on various cancer cell lines.

Results: The National Cancer Institute’s preliminary anticancer screening results showed compounds 4b and 5b having potent antileukemic activity. Compound 4b selectively showed 32 percent lethality on Human Leukemia-60 cell line. The docking studies of the derivatives on aromatase enzyme (Protein Data Bank: 3S7S) have shown reversible interactions at the active site with good docking scores comparable to Letrozole and Exemestane. Furthermore, the selected derivatives were tested for anticancer activity on HeLa cell line based on the molecular docking studies.

Conclusion: Compounds 4b and 5b showed effective inhibition equivalent to Letrozole. These preliminary biological screening studies have given positive anticancer activity for these new classes of derivatives. An additional research study like the mechanism of action of the anticancer activity of this new class of compounds is necessary. These groundwork studies illuminate a future pathway for research of this class of compounds enabling the discovery of potent antitumor agents.

Keywords: 1, 3, 4-thiadiazole, benzothiazole, imidazo[2, 1-b][1, 3, 4]thiadiazole, letrozole, anticancer activity, aromatase, docking.

Graphical Abstract
[1]
Fact Sheet World Health Organization. Cancer Key Facts., https://www.who.int/news-room/fact-sheets/detail/cancer [20 January 2019].
[2]
Ali, R.; Mirza, Z.; Ashraf, G.M.; Kamal, M.A.; Ansari, S.A.; Damanhouri, G.A.; Abuzenadah, A.M.; Chaudhary, A.G.; Sheikh, I.A. New anticancer agents: recent developments in tumor therapy. Anticancer Res., 2012, 32(7), 2999-3005.
[PMID: 22753764]
[3]
Lønning, P.E.; Knappskog, S. Mapping genetic alterations causing chemoresistance in cancer: identifying the roads by tracking the drivers. Oncogene, 2013, 32(46), 5315-5330.
[http://dx.doi.org/10.1038/onc.2013.48] [PMID: 23474753]
[4]
Hosseinzadeh, Z.; Ramazani, A.; Razzaghi-Asl, N. Anti-cancer nitrogen-containing heterocyclic compounds. Curr. Org. Chem., 2018, 22, 2256-2279.
[http://dx.doi.org/10.2174/1385272822666181008142138]
[5]
Jain, A.K.; Sharma, S.; Vaidya, A.; Ravichandran, V.; Agrawal, R.K. 1,3,4-thiadiazole and its derivatives: a review on recent progress in biological activities. Chem. Biol. Drug Des., 2013, 81(5), 557-576.
[http://dx.doi.org/10.1111/cbdd.12125] [PMID: 23452185]
[6]
Lata; Kushwaha, K.; Gupta, A.; Meena, D.; Verma, A.; Biological activities of imidazo[2,1-b][1,3,4]thiadiazole derivatives: A review. Heterocyclic Lett., 2015, 5, 489-509.
[7]
Gadad, A.K.; Karki, S.S.; Rajurkar, V.G.; Bhongade, B.A. Synthesis and biological evaluation of 6-aryl-N-[(dimethylamino)methylene]-5-formylimidazo[2,1-b]-1,3,4-thiadiazole-2-sulfonamides as antitumor agents. Arzneimittelforschung, 1999, 49, 858-863.
[PMID: 10554665]
[8]
Terzioglu, N.; Gürsoy, A. Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazide. Eur. J. Med. Chem., 2003, 38(7-8), 781-786.
[http://dx.doi.org/10.1016/S0223-5234(03)00138-7] [PMID: 12932910]
[9]
Andreani, A.; Leoni, A.; Locatelli, A.; Morigi, R.; Rambaldi, M.; Recanatini, M.; Garaliene, V. Potential antitumor agents. Part 29(1): synthesis and potential coanthracyclinic activity of imidazo[2,1-b]thiazole guanylhydrazones. Bioorg. Med. Chem., 2000, 8(9), 2359-2366.
[http://dx.doi.org/10.1016/S0968-0896(00)00165-6] [PMID: 11026549]
[10]
Lee, Y.R.; Jin, G.H.; Lee, S.M.; Park, J.W.; Ryu, J.H.; Jeon, R.; Park, B.H. Inhibition of TNF-α-mediated inflammatory responses by a benzodioxolylacetylamino-linked benzothiazole analog in human fibroblast-like synoviocytes. Biochem. Biophys. Res. Commun., 2011, 408(4), 625-629.
[http://dx.doi.org/10.1016/j.bbrc.2011.04.073] [PMID: 21530496]
[11]
Kamal, A.; Srikanth, Y.V.; Naseer Ahmed Khan, M.; Ashraf, M.; Kashi Reddy, M.; Sultana, F.; Kaur, T.; Chashoo, G.; Suri, N.; Sehar, I.; Wani, Z.A.; Saxena, A.; Sharma, P.R.; Bhushan, S.; Mondhe, D.M.; Saxena, A.K. 2-Anilinonicotinyl linked 2-amino-benzothiazoles and [1,2,4]triazolo[1,5-b] [1,2,4]benzothiadiazine conjugates as potential mitochondrial apoptotic inducers. Bioorg. Med. Chem., 2011, 19(23), 7136-7150.
[http://dx.doi.org/10.1016/j.bmc.2011.09.060] [PMID: 22047801]
[12]
Kamal, A.; Reddy, K.S.; Khan, M.N.; Shetti, R.V.; Ramaiah, M.J.; Pushpavalli, S.N.; Srinivas, C.; Pal-Bhadra, M.; Chourasia, M.; Sastry, G.N.; Juvekar, A.; Zingde, S.; Barkume, M. Synthesis, DNA-binding ability and anticancer activity of benzothiazole/benzoxazole-pyrrolo[2,1-c][1,4]benzodiazepine conjugates. Bioorg. Med. Chem., 2010, 18(13), 4747-4761.
[http://dx.doi.org/10.1016/j.bmc.2010.05.007] [PMID: 20627593]
[13]
Tasler, S.; Müller, O.; Wieber, T.; Herz, T.; Pegoraro, S.; Saeb, W.; Lang, M.; Krauss, R.; Totzke, F.; Zirrgiebel, U.; Ehlert, J.E.; Kubbutat, M.H.; Schächtele, C. Substituted 2-arylbenzothiazoles as kinase inhibitors: hit-to-lead optimization. Bioorg. Med. Chem., 2009, 17(18), 6728-6737.
[http://dx.doi.org/10.1016/j.bmc.2009.07.047] [PMID: 19692247]
[14]
Aliabadi, A. 1,3,4-thiadiazole based anticancer agents. Anticancer. Agents Med. Chem., 2016, 16(10), 1301-1314.
[http://dx.doi.org/10.2174/1871520616666160628100936] [PMID: 27484056]
[15]
Ibrahim, D.A. Synthesis and biological evaluation of 3,6-disubstituted [1,2,4]triazolo[3,4-b][1,3,4]thiadiazole derivatives as a novel class of potential anti-tumor agents. Eur. J. Med. Chem., 2009, 44(7), 2776-2781.
[http://dx.doi.org/10.1016/j.ejmech.2009.01.003] [PMID: 19203813]
[16]
Al-Tel, T.H.; Al-Qawasmeh, R.A.; Zaarour, R. Design, synthesis and in vitro antimicrobial evaluation of novel Imidazo[1,2-a]pyridine and imidazo[2,1-b][1,3]benzothiazole motifs. Eur. J. Med. Chem., 2011, 46(5), 1874-1881.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.051] [PMID: 21414694]
[17]
Deng, X.Q.; Song, M.X.; Wei, C.X.; Li, F.N.; Quan, Z.S. Synthesis and anticonvulsant activity of 7-alkoxy-triazolo-[3, 4-b]benzo[d]thiazoles. Med. Chem., 2010, 6(5), 313-320.
[http://dx.doi.org/10.2174/157340610793358855] [PMID: 20977415]
[18]
Amnerkar, N.D.; Bhusari, K.P. Synthesis, anticonvulsant activity and 3D-QSAR study of some prop-2-eneamido and 1-acetyl-pyrazolin derivatives of aminobenzothiazole. Eur. J. Med. Chem., 2010, 45(1), 149-159.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.037] [PMID: 19853976]
[19]
Sreenivasa, G.M.; Jayachandran, E.; Shivakumar, B.; Kumar, J.K.; Kumar, V.M.M.J. Synthesis of bioactive molecule fluoro benzothiazole comprising potent heterocyclic moieties for anthelmintic activity. Arch. Pharm. Res., 2009, 1, 150-157.
[20]
Choi, M.M.; Kim, E.A.; Hahn, H.G.; Nam, K.D.; Yang, S.J.; Choi, S.Y.; Kim, T.U.; Cho, S.W.; Huh, J.W. Protective effect of benzothiazole derivative KHG21834 on amyloid beta-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons. Toxicology, 2007, 239(3), 156-166.
[http://dx.doi.org/10.1016/j.tox.2007.07.010] [PMID: 17714846]
[21]
Jimonet, P.; Audiau, F.; Barreau, M.; Blanchard, J.C.; Boireau, A.; Bour, Y.; Coléno, M.A.; Doble, A.; Doerflinger, G.; Huu, C.D.; Donat, M.H.; Duchesne, J.M.; Ganil, P.; Guérémy, C.; Honor, E.; Just, B.; Kerphirique, R.; Gontier, S.; Hubert, P.; Laduron, P.M.; Le Blevec, J.; Meunier, M.; Miquet, J.M.; Nemecek, C.; Mignani, S.; Piot, O.; Pratt, J.; Rataud, J.; Reibaud, M.; Stutzmann, J.M.; Mignani, S. Riluzole series. Synthesis and in vivo “antiglutamate” activity of 6-substituted-2-benzothiazolamines and 3-substituted-2-imino-benzothiazolines. J. Med. Chem., 1999, 42(15), 2828-2843.
[http://dx.doi.org/10.1021/jm980202u] [PMID: 10425092]
[22]
Bowyer, P.W.; Gunaratne, R.S.; Grainger, M.; Withers-Martinez, C.; Wickramsinghe, S.R.; Tate, E.W.; Leatherbarrow, R.J.; Brown, K.A.; Holder, A.A.; Smith, D.F. Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum. Biochem. J., 2007, 408(2), 173-180.
[http://dx.doi.org/10.1042/BJ20070692] [PMID: 17714074]
[23]
Huang, Q.; Mao, J.; Wan, B.; Wang, Y.; Brun, R.; Franzblau, S.G.; Kozikowski, A.P. Searching for new cures for tuberculosis: design, synthesis, and biological evaluation of 2-methylbenzothiazoles. J. Med. Chem., 2009, 52(21), 6757-6767.
[http://dx.doi.org/10.1021/jm901112f] [PMID: 19817445]
[24]
Li, Y.; Geng, J.; Liu, Y.; Yu, S.; Zhao, G. Thiadiazole-a promising structure in medicinal chemistry. ChemMedChem, 2013, 8(1), 27-41.
[http://dx.doi.org/10.1002/cmdc.201200355] [PMID: 23208773]
[25]
Hu, Y.; Li, C.Y.; Wang, X.M.; Yang, Y.H.; Zhu, H.L. 1,3,4-Thiadiazole: synthesis, reactions, and applications in medicinal, agricultural, and materials chemistry. Chem. Rev., 2014, 114(10), 5572-5610.
[http://dx.doi.org/10.1021/cr400131u] [PMID: 24716666]
[26]
Matysiak, J. Biological and pharmacological activities of 1,3,4-thiadiazole based compounds. Mini Rev. Med. Chem., 2015, 15(9), 762-775.
[http://dx.doi.org/10.2174/1389557515666150519104057] [PMID: 25985954]
[27]
Haider, S.; Alam, M.S.; Hamid, H. 1,3,4-Thiadiazoles: a potent multi targeted pharmacological scaffold. Eur. J. Med. Chem., 2015, 92, 156-177.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.035] [PMID: 25553540]
[28]
Dawood, K.M.; Farghaly, T.A. Thiadiazole inhibitors: a patent review. Expert Opin. Ther. Pat., 2017, 27(4), 477-505.
[http://dx.doi.org/10.1080/13543776.2017.1272575] [PMID: 27976971]
[29]
Senff-Ribeiro, A.; Echevarria, A.; Silva, E.F.; Veiga, S.S.; Oliveira, M.B. Antimelanoma activity of 1,3,4-thiadiazolium mesoionics: a structure-activity relationship study. Anticancer Drugs, 2004, 15(3), 269-275.
[http://dx.doi.org/10.1097/00001813-200403000-00012] [PMID: 15014361]
[30]
Juszczak, M.; Matysiak, J.; Szeliga, M.; Pożarowski, P.; Niewiadomy, A.; Albrecht, J.; Rzeski, W. 2-Amino-1,3,4-thiadiazole derivative (FABT) inhibits the extracellular signal-regulated kinase pathway and induces cell cycle arrest in human non-small lung carcinoma cells. Bioorg. Med. Chem. Lett., 2012, 22(17), 5466-5469.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.036] [PMID: 22877634]
[31]
Zhang, K.; Wang, P.; Xuan, L.N.; Fu, X.Y.; Jing, F.; Li, S.; Liu, Y.M.; Chen, B.Q. Synthesis and antitumor activities of novel hybrid molecules containing 1,3,4-oxadiazole and 1,3,4-thiadiazole bearing Schiff base moiety. Bioorg. Med. Chem. Lett., 2014, 24(22), 5154-5156.
[http://dx.doi.org/10.1016/j.bmcl.2014.09.086] [PMID: 25442303]
[32]
Yadagiri, B.; Gurrala, S.; Bantu, R.; Nagarapu, L.; Polepalli, S.; Srujana, G.; Jain, N. Synthesis and evaluation of benzosuberone embedded with 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole moieties as new potential anti proliferative agents. Bioorg. Med. Chem. Lett., 2015, 25(10), 2220-2224.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.032] [PMID: 25827522]
[33]
Kumar, D.; Kumar, N.M.; Noel, B.; Shah, K. A series of 2-arylamino-5-(indolyl)-1,3,4-thiadiazoles as potent cytotoxic agents. Eur. J. Med. Chem., 2012, 55, 432-438.
[http://dx.doi.org/10.1016/j.ejmech.2012.06.047] [PMID: 22818039]
[34]
Guan, P.; Sun, F.; Hou, X.; Wang, F.; Yi, F.; Xu, W.; Fang, H. Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors. Bioorg. Med. Chem., 2012, 20(12), 3865-3872.
[http://dx.doi.org/10.1016/j.bmc.2012.04.032] [PMID: 22579621]
[35]
Li, Y.J.; Qin, Y.J.; Makawana, J.A.; Wang, Y.T.; Zhang, Y.Q.; Zhang, Y.L.; Yang, M.R.; Jiang, A.Q.; Zhu, H.L. Synthesis, biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents. Bioorg. Med. Chem., 2014, 22(15), 4312-4322.
[http://dx.doi.org/10.1016/j.bmc.2014.05.017] [PMID: 24909678]
[36]
Guan, P.; Wang, L.; Hou, X.; Wan, Y.; Xu, W.; Tang, W.; Fang, H. Improved antiproliferative activity of 1,3,4-thiadiazole-containing histone deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif. Bioorg. Med. Chem., 2014, 22(21), 5766-5775.
[http://dx.doi.org/10.1016/j.bmc.2014.09.039] [PMID: 25311567]
[37]
Radi, M.; Crespan, E.; Botta, G.; Falchi, F.; Maga, G.; Manetti, F.; Corradi, V.; Mancini, M.; Santucci, M.A.; Schenone, S.; Botta, M. Discovery and SAR of 1,3,4-thiadiazole derivatives as potent Abl tyrosine kinase inhibitors and cytodifferentiating agents. Bioorg. Med. Chem. Lett., 2008, 18(3), 1207-1211.
[http://dx.doi.org/10.1016/j.bmcl.2007.11.112] [PMID: 18078752]
[38]
Hosseinzadeh, L.; Khorand, A.; Aliabadi, A. Discovery of 2-phenyl-N-(5-(trifluoromethyl)-1,3,4-thiadiazol-2-yl)acetamide derivatives as apoptosis inducers via the caspase pathway with potential anticancer activity. Arch. Pharm. (Weinheim), 2013, 346(11), 812-818.
[http://dx.doi.org/10.1002/ardp.201300180] [PMID: 24123162]
[39]
Chou, J.Y.; Lai, S.Y.; Pan, S.L.; Jow, G.M.; Chern, J.W.; Guh, J.H. Investigation of anticancer mechanism of thiadiazole-based compound in human non-small cell lung cancer A549 cells. Biochem. Pharmacol., 2003, 66(1), 115-124.
[http://dx.doi.org/10.1016/S0006-2952(03)00254-5] [PMID: 12818371]
[40]
LoRusso, P.M.; Goncalves, P.H.; Casetta, L.; Carter, J.A.; Litwiler, K.; Roseberry, D.; Rush, S.; Schreiber, J.; Simmons, H.M.; Ptaszynski, M.; Sausville, E.A. First-in-human phase 1 study of filanesib (ARRY-520), a kinesin spindle protein inhibitor, in patients with advanced solid tumors. Invest. New Drugs, 2015, 33(2), 440-449.
[http://dx.doi.org/10.1007/s10637-015-0211-0] [PMID: 25684345]
[41]
Mortimer, C.G.; Wells, G.; Crochard, J.P. Stone, E.L.; Bradshaw, T.D.; Stevens, M.F.G.; Westwell, A.D.; Antitumour benzothiazoles. 26.(1) 2-(3,4-dimethoxyphenyl)-5- fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J. Med. Chem., 2006, 49, 179-185.
[http://dx.doi.org/10.1021/jm050942k] [PMID: 16392802]
[42]
Rouf, A.; Tanyeli, C. Bioactive thiazole and benzothiazole derivatives. Eur. J. Med. Chem., 2015, 97, 911-927.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.058] [PMID: 25455640]
[43]
Noolvi, M.N.; Patel, H.M.; Kaur, M. Benzothiazoles: search for anticancer agents. Eur. J. Med. Chem., 2012, 54, 447-462.
[http://dx.doi.org/10.1016/j.ejmech.2012.05.028] [PMID: 22703845]
[44]
Keri, R.S.; Patil, M.R.; Patil, S.A.; Budagumpi, S. A comprehensive review in current developments of benzothiazole-based molecules in medicinal chemistry. Eur. J. Med. Chem., 2015, 89, 207-251.
[http://dx.doi.org/10.1016/j.ejmech.2014.10.059] [PMID: 25462241]
[45]
Sharma, P.C.; Sinhmar, A.; Sharma, A.; Rajak, H.; Pathak, D.P. Medicinal significance of benzothiazole scaffold: an insight view. J. Enzyme Inhib. Med. Chem., 2013, 28(2), 240-266.
[http://dx.doi.org/10.3109/14756366.2012.720572] [PMID: 23030043]
[46]
Singh, M.; Singh, S.K. Benzothiazoles: how relevant in cancer drug design strategy? Anticancer. Agents Med. Chem., 2014, 14(1), 127-146.
[http://dx.doi.org/10.2174/18715206113139990312] [PMID: 23869774]
[47]
Turan-Zitouni, G.; Özkay, Y.; Özdemir, A.; Kaplancıklı, Z.A.; Altıntop, M.D. Synthesis of some benzothiazole based piperazinedithiocarbamate derivatives and evaluation of their anticancer activities. Lett. Drug Des. Discov., 2011, 8, 830-837.
[http://dx.doi.org/10.2174/157018011797200786]
[48]
Abbot, V.; Sharma, P.; Dhiman, S.; Noolvi, M.N.; Patel, H.M.; Bhardwaj, V. Small hybrid heteroaromatics: resourceful biological tools in cancer research. RSC Advances, 2017, 7, 28313-28349.
[http://dx.doi.org/10.1039/C6RA24662A]
[49]
Patel, H.M.; Bari, P.; Karpoormath, R.; Noolvi, M.N.; Thapliyal, N.; Surana, S.; Jain, P. Design and synthesis of VEGFR-2 tyrosine kinase inhibitors as potential anticancer agents by virtual based screening. RSC Advances, 2015, 5, 56724-56771.
[http://dx.doi.org/10.1039/C5RA05277G]
[50]
Patel, H.M.; Sing, B.; Bhardwaj, V.; Palkar, M.; Shaikh, M.S.; Rane, R.; Alwan, W.S.; Gadad, A.K.; Noolvi, M.N.; Karpoormath, R. Design, synthesis and evaluation of small molecule imidazo[2,1-b][1,3,4]thiadiazoles as inhibitors of transforming growth factor-β type-I receptor kinase (ALK5). Eur. J. Med. Chem., 2015, 93, 599-613.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.002] [PMID: 25234355]
[51]
Noolvi, M.N.; Patel, H.M.; Kamboj, S.; Kaur, A.; Mann, V. 2,6-disubstituted imidazo[2,1,b]-1,3,4-thiadizoles: Search for anticancer agents. Eur. J. Med. Chem., 2012, 56, 56-69.
[http://dx.doi.org/10.1016/j.ejmech.2012.08.012] [PMID: 22960694]
[52]
Pradeepkiran, J.A.; Reddy, P.H. Structure Based Design and Molecular Docking Studies for Phosphorylated Tau Inhibitors in Alzheimer’s Disease. Cells, 2019, 8(3), 260-286.
[http://dx.doi.org/10.3390/cells8030260] [PMID: 30893872]
[53]
Pradeepkiran, J.A.; Reddy, A.P.; Reddy, P.H. Pharmacophore-based models for therapeutic drugs against phosphorylated tau in Alzheimer’s disease. Drug Discovery. Today, 2019, 24(2), 616-623.
[http://dx.doi.org/10.1016/j.drudis.2018.11.005]
[54]
Munir, A.; Azam, S.; Mehmood, A.; Khan, Z.; Khan, A.M.; Fazal, S. Structure-based pharmacophore modeling, virtual screening and molecular docking for the treatment of ESR1 mutations in breast cancer. Drug Designing: Open Access, 2016, 51, 000137.
[http://dx.doi.org/10.4172/2169-0138.1000137]
[55]
Neves, M.A.C.; Dinis, T.C.P.; Colombo, G.; Sá e Melo, M.L. Fast three dimensional pharmacophore virtual screening of new potent non-steroid aromatase inhibitors. J. Med. Chem., 2009, 52(1), 143-150.
[http://dx.doi.org/10.1021/jm800945c] [PMID: 19072235]
[56]
Sun, J.; Yang, Y.S.; Li, W.; Zhang, Y.B.; Wang, X.L.; Tang, J.F.; Zhu, H.L. Synthesis, biological evaluation and molecular docking studies of 1,3,4-thiadiazole derivatives containing 1,4-benzodioxan as potential antitumor agents. Bioorg. Med. Chem. Lett., 2011, 21(20), 6116-6121.
[http://dx.doi.org/10.1016/j.bmcl.2011.08.039] [PMID: 21889345]
[57]
Park, J.; Czapla, L.; Amaro, R.E. Molecular simulations of aromatase reveal new insights into the mechanism of ligand binding. J. Chem. Inf. Model., 2013, 53(8), 2047-2056.
[http://dx.doi.org/10.1021/ci400225w] [PMID: 23927370]
[58]
Muftuoglu, Y.; Mustata, G. Pharmacophore modeling strategies for the development of novel nonsteroidal inhibitors of human aromatase (CYP19). Bioorg. Med. Chem. Lett., 2010, 20(10), 3050-3064.
[http://dx.doi.org/10.1016/j.bmcl.2010.03.113] [PMID: 20413308]
[59]
Naravut, S.; Chanin, N.; Chartchalerm, I.N.A.; Virapong, P. Molecular Docking of Aromatase Inhibitors. Molecules, 2011, 16, 3597-3617.
[http://dx.doi.org/10.3390/molecules16053597]
[60]
Stefanachi, A.; Favia, A.D.; Nicolotti, O.; Leonetti, F.; Pisani, L.; Catto, M.; Zimmer, C.; Hartmann, R.W.; Carotti, A. Design, synthesis, and biological evaluation of imidazolyl derivatives of 4,7-disubstituted coumarins as aromatase inhibitors selective over 17-α-hydroxylase/C17-20 lyase. J. Med. Chem., 2011, 54(6), 1613-1625.
[http://dx.doi.org/10.1021/jm101120u] [PMID: 21341743]
[61]
Galeazzi, R.; Massaccesi, L. Insight into the binding interactions of CYP450 aromatase inhibitors with their target enzyme: a combined molecular docking and molecular dynamics study. J. Mol. Model., 2012, 18(3), 1153-1166.
[http://dx.doi.org/10.1007/s00894-011-1144-y] [PMID: 21681442]
[62]
Nagar, S.; Saha, A. Exploring benzcyclo derivatives as potent aromatase inhibitors using ligand-based modeling studies. Eur. J. Med. Chem., 2010, 45(9), 4307-4315.
[http://dx.doi.org/10.1016/j.ejmech.2010.06.033] [PMID: 20638757]
[63]
Jiang, W.; Ghosh, D. Motion and flexibility in human cytochrome p450 aromatase. PLoS One, 2012, 7(2), e32565.
[http://dx.doi.org/10.1371/journal.pone.0032565] [PMID: 22384274]
[64]
Sgrignani, J.; Bon, M.; Colombo, G.; Magistrato, A. Computational approaches elucidate the allosteric mechanism of human aromatase inhibition: a novel possible route to Small-molecule regulation of CYP450s activities? J. Chem. Inf. Model., 2014, 54(10), 2856-2868.
[http://dx.doi.org/10.1021/ci500425y] [PMID: 25178092]
[65]
Narayana, B.L.; Pran Kishore, D.; Balakumar, C.; Rao, K.V.; Kaur, R.; Rao, A.R.; Murthy, J.N.; Ravikumar, M. Molecular modeling evaluation of non-steroidal aromatase inhibitors. Chem. Biol. Drug Des., 2012, 79(5), 674-682.
[http://dx.doi.org/10.1111/j.1747-0285.2011.01277.x] [PMID: 22129073]
[66]
Bradshaw, T.D.; Westwell, A.D. The development of the antitumour benzothiazole prodrug, Phortress, as a clinical candidate. Curr. Med. Chem., 2004, 11(8), 1009-1021.
[http://dx.doi.org/10.2174/0929867043455530] [PMID: 15078163]
[67]
Thienpont, D.; Vanparijs, O.F.; Raeymaekers, A.H.M.; Vandenberk, J.; Demoen, J.A.; Allewijn, F.T.N.; Marsboom, R.P.H.; Niemegeers, C.J.E.; Schellekens, K.H.; Janssen, P.A. Tetramisole (R 8299), a new, potent broad spectrum anthelmintic. Nature, 1966, 209(5028), 1084-1086.
[http://dx.doi.org/10.1038/2091084a0] [PMID: 5925183]
[68]
Manjula, S.N.; Malleshappa Noolvi, N.; Vipan Parihar, K.; Manohara Reddy, S.A.; Ramani, V.; Gadad, A.K.; Singh, G.; Gopalan Kutty, N.; Mallikarjuna Rao, C. Synthesis and antitumor activity of optically active thiourea and their 2-aminobenzothiazole derivatives: a novel class of anticancer agents. Eur. J. Med. Chem., 2009, 44(7), 2923-2929.
[http://dx.doi.org/10.1016/j.ejmech.2008.12.002] [PMID: 19128861]
[69]
Alley, M.C.; Scudiero, D.A.; Monks, A.; Hursey, M.L.; Czerwinski, M.J.; Fine, D.L.; Abbott, B.J.; Mayo, J.G.; Shoemaker, R.H.; Boyd, M.R. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res., 1988, 48(3), 589-601.
[PMID: 3335022]
[70]
Grever, M.R.; Schepartz, S.A.; Chabner, B.A. The National Cancer Institute: cancer drug discovery and development program. Semin. Oncol., 1992, 19(6), 622-638.
[PMID: 1462164]
[71]
Boyd, M.R.; Paul, K.D. Some practical considerations and applications of the national cancer institute in vitro anticancer drug discovery screen. Drug Dev. Res., 1995, 19, 91-110.
[http://dx.doi.org/10.1002/ddr.430340203]
[72]
RCSB. Protein Data Bank: Crystal structure of human placental aromatase complexed with breast cancer drug exemestane: 3S7S, https://www.rcsb.org/structure/3s7s [January 23, 2020];
[73]
Ghosh, D.; Griswold, J.; Erman, M.; Pangborn, W. Structural basis for androgen specificity and oestrogen synthesis in human aromatase. Nature, 2009, 457(7226), 219-223.
[http://dx.doi.org/10.1038/nature07614] [PMID: 19129847]
[74]
Maestro, v93; Schrödinger, LLC: New York, NY, 2012.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy