Synthesis and screening of novel 2,4-bis substituted quinazolines as tubulin polymerization promoters and antiproliferative agents.

IF 4.1 4区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY RSC medicinal chemistry Pub Date : 2025-01-15 DOI:10.1039/d4md00755g

Ashish Ranjan Dwivedi, Vijay Kumar, Vikash Prashar, Kailash Jangid, Naveen Kumar, Bharti Devi, Jyoti Parkash, Vinod Kumar

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Abstract

Twelve 2,4-bis-substituted quinazoline-based compounds were synthesized and screened for antiproliferative and tubulin polymerization enhancing potential. In the series, compound A4V-3 substituted with an imidazole ring displayed IC₅₀ values of 4.25 μM, 2.65 μM, and 9.95 μM, and A4V-5 with a benzotriazole substitution displayed IC₅₀ values of 3.45 μM, 7.25 μM, and 8.14 μM against MCF-7, HCT-116 and SHSY-5Y cancer cells, respectively. In the mechanistic studies involving cell cycle analysis, apoptosis assay and JC-1 studies, compound A4V-3 was found to arrest the cells in the G₂/M phase of the cell cycle and induce mitochondria-mediated apoptosis. In addition, compound A4V-3 displayed significant tubulin polymerization-enhancing potential. 2,4-Bis-substituted quinazoline-based compounds showed appreciable drug-like characteristics and can be developed as potent anticancer agents.

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