Synthesis of New 1, 3, 4-Oxadiazole-Incorporated 1, 2, 3-Triazole Moieties as Potential Anticancer Agents Targeting Thymidylate Synthase and Their Docking Studies

Pharmaceuticals
Mohammad Mahboob AlamSyed Nazreen

Abstract

Thymidylate synthase (TS) has emerged as a hot spot in cancer treatment, as it is directly involved in DNA synthesis. In the present article, nine hybrids containing 1,2,3-triazole and 1,3,4-oxadiazole moieties (6-14) were synthesized and evaluated for anticancer and in vitro thymidylate synthase activities. According to in silico pharmacokinetic studies, the synthesized hybrids exhibited good drug likeness properties and bioavailability. The cytotoxicity results indicated that compounds 12 and 13 exhibited remarkable inhibition on the tested Michigan Cancer Foundation (MCF-7) and Human colorectal Carcinoma (HCT-116) cell lines. Compound 12 showed four-fold inhibition to a standard drug, 5-fluoruracil, and comparable inhibition to tamoxifen, whereas compound 13 exerted five-fold activity of tamoxifen and 24-fold activity of 5-fluorouracil for MCF-7 cells. Compounds 12 and 13 inhibited thymidylate synthase enzyme, with an half maximal inhibitory concentration, IC50 of 2.52 µM and 4.38 µM, while a standard drug, pemetrexed, showed IC50 = 6.75 µM. The molecular docking data of compounds 12 and 13 were found to be in support of biological activities data. In conclusion, hybrids (12 and 13) may inhibit thymidylate synthase enzyme, w...Continue Reading

References

Jan 1, 1995·Annual Review of Biochemistry·C W Carreras, D V Santi
May 31, 2002·Journal of Medicinal Chemistry·Daniel F VeberKenneth D Kopple
Jun 3, 2008·Bioorganic & Medicinal Chemistry Letters·F Esra OnenJean Herscovici
Sep 8, 2010·European Journal of Medicinal Chemistry·Keshari Kishore JhaPriyanka Singh
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
Apr 26, 2011·Methods in Molecular Biology·Johan van MeerlooJacqueline Cloos
Feb 15, 2012·Expert Opinion on Therapeutic Patents·Pablo ÁlvarezAntonia Aranega
Sep 10, 2014·Cancers·Genevieve HousmanSibaji Sarkar
Aug 16, 2016·European Journal of Medicinal Chemistry·Alessia CatalanoStefano Mangani
Oct 27, 2017·Advanced Pharmaceutical Bulletin·Behzad MansooriBehzad Baradaran
Nov 15, 2019·Nature·Neil VasanDavid M Hyman
May 2, 2020·Journal of Enzyme Inhibition and Medicinal Chemistry·Zohor Mohammad Mahdi AlzhraniSyed Nazreen
Aug 1, 2020·Bioorganic & Medicinal Chemistry Letters·Sergio PinheiroSandro J Greco

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