Issue 7, 2024

Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer

Abstract

Considering the promising effects of molecular hybridization on drug discovery in recent years and the ongoing endeavors to develop bioactive scaffolds tethering the 1,2,3-triazole core, the present study sought to investigate whether the 1,2,3-triazole-linked chromene and benzene sulfonamide nucleus could exhibit activity against the human breast cancer cell line MCF-7 and prostate cancer cell line PC-3. To this end, three focused bioactive series of mono- and -bis-1,2,3-triazoles were effectively synthesized via copper-assisted cycloaddition of mono- and/or di-alkyne chromenone derivatives 2a and b and 9 with several sulfa drug azides 4a–d and 6. The resulting molecular derivatives were tested for cytotoxicity against prostate and breast cancer cells. Among the derivatives, 10a, 10c, and 10e exhibited potent cytotoxicity against PC-3 cells with IC50 values of 2.08, 7.57, and 5.52 μM compared to doxorubicin (IC50 = 2.31 μM) with potent inhibition of CA IX with IC50 values of 0.113, 0.134, and 0.214 μM. The most active compound, 10a, was tested for apoptosis-induction; it induced apoptosis by 31.9-fold cell cycle arrest at the G1-phase. Further, the molecular modeling approach highlighted the relevant binding affinity for the top-active compound 10a against CA IX as one of the most prominent PC-3 prostate cancer-associated biotargets.

Graphical abstract: Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer

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Article information

Article type
Research Article
Submitted
27 Apr 2024
Accepted
07 Jun 2024
First published
24 Jun 2024

RSC Med. Chem., 2024,15, 2440-2461

Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer

F. F. Albelwi, M. S. Nafie, N. R. Albujuq, W. Hourani, A. Aljuhani, K. M. Darwish, M. M. Tawfik, N. Rezki and M. R. Aouad, RSC Med. Chem., 2024, 15, 2440 DOI: 10.1039/D4MD00302K

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