Main Article Content
The cancer is the world's most silent and life-threatening diseases, which may arise in most common people without any indication at any age and result in uncontrolled growth and metastasis. In the current manuscript, we targeted the discovery of novel carbonic anhydrase IX inhibitors. The discovery is based on computational techniques based on direct and indirect drug design. We screened nearly 500000 compounds from the zinc database to identify the top 1000 compounds with indirect drug design techniques while the top 200 were docked for the interactions and scoring functions. The top 12 out of these were reported in the manuscript, which showed higher binding scores than the standard compounds with selectivity based on interaction. These leads may be the future drugs for anticancer agents through carbonic anhydrase inhibitors.
New Global Cancer Data: GLOBOCAN; 2018.
Mareel M, Leroy A. Clinical, cellular and molecular aspects of cancer invasion. Physiol. Rev. 2003;83:337–376.
Supuran CT. Carbonic anhydrases: Novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discovery. 2008;7:168–181.
Alterio V, Di Fiore A, D’Ambrosio K, Supuran CT, De Simone G. Multiple binding modes of inhibitors to carbonic anhydrases: How to design specific drugs targeting 15 different isoforms? Chem. Rev. 2012;112:4421–4468.
Supuran CT, Alterio V, Di Fiore A, Ambrosio KD, Carta F, Monti SM, De Simone G. Inhibition of carbonic anhydrase IX targets primary tumors, metastases and cancer stem cells: Three for the price of one. Med. Res. Rev. 2018;38:1799–1836.
Wykoff CC, Beasley NJ, Watson PH, Turner KJ, Pastorek J, Sibtain A, Wilson GD, Turley H, Talks KL, Maxwell PH, Pugh CW, Ratcliffe PJ, Harris AL. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res. 2000;60:7075–7083.
Ivanov S, Liao SY, Ivanova A, Danilkovitch-Miagkova A, Tarasova N, Weirich G, Merrill MJ, Proescholdt MA, Oldfield EH, Lee J, Zavada J, Waheed A, Sly W, Lerman MI, Stanbridge EJ. Expression of hypoxia-inducible cell-surface transmembrane carbonic anhydrases in human cancer. Am. J. Pathol. 2001;158:905–919.
Peng XM, Damu GLV, Zhou CH. Current developments of coumarin compounds in medicinal chemistry. Curr. Pharm. Des. 2013;19:3884–3930.
Thakur A, Singla R, Jaitak V. Coumarins as anticancer agents: A review on synthetic strategies, mechanism of action and SAR studies. Eur. J. Med. Chem. 2015;101:476–495.
Emami S, Dadashpour S. Current developments of coumarin-based anti-cancer agents in medicinal chemistry. Eur. J. Med. Chem. 2015;102:611–630.
Bua Silvia, et al. A sweet combination: Developing saccharin and acesulfame K structures for selectively targeting the tumor-associated carbonic anhydrases IX and XII. Journal of Medicinal Chemistry. 2020;63(1):321-333.
Maresca A, Supuran CT. Coumarins incorporating hydroxy- and chloro-moieties selectively inhibit the transmembrane, tumor-associated carbonic anhydraseisoforms IX and XII over the cytosolic ones I and II. Bioorg. Med. Chem. Lett. 2010;20:4511–4514.
Thomsen R, Christensen MH. MolDock: A new technique for high-accuracy molecular docking. J Med Chem. 2006;49:3315-3321.
Gehlhaar DK, Bouzida D, Rejto PA. Fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases. International Conference on Evolutionary Programming, City; Springer. 1998;449-461.
Ahmad Khurshid, et al. Targeting Caspase 8: Using structural and ligand-based approaches to identify potential leads for the treatment of multi-neurodegenerative diseases. Molecules (Basel, Switzerland). 2019;24(9);1827.
Saeed Mohd, et al. Predicted binding of certain antifilarial compounds with glutathione-S-transferase of human Filariids. Bioinformation. 2013;9(5):233- 7.
Balaramnavar VM, et al. Eur J Med Chem. 2014;87:578.