Design, synthesis, in silico studies, and apoptotic antiproliferative activity of novel thiazole-2-acetamide derivatives as tubulin polymerization inhibitors DOI Creative Commons

Lamya H. Al-Wahaibi,

Ali M. Elshamsy,

Taha F. S. Ali

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 16, 2025

Tubulin polymerization inhibitors have emerged as interesting anticancer therapies. We present the design, synthesis, and structural elucidation of novel thiazole-based derivatives to identify tubulin with potent antiproliferative efficacy strong inhibition polymerization. The compounds consist two scaffolds. Scaffold A 10a-e scaffold B 13a-e. structures newly synthesized 13a-e were validated using 1H NMR, 13C elemental analysis. most effective antitubulin derivative was 10a, exhibiting an IC50 value 2.69 μM. Subsequently, 10o 13d exhibited values 3.62 μM 3.68 μM, respectively. These more potency than reference combretastatin A-4, which displayed 8.33 had no cytotoxic effects on normal cells, preserving over 85% cell viability at 50 experiment demonstrated that 10o, significant activity against four cancer lines, average GI50 6, 7, 8 equivalent reference's doxorubicin sorafenib. Compounds activate caspases 3, 9, Bax, while down-regulating anti-apoptotic protein Bcl2. Molecular docking studies superior binding affinities for 10a (-7.3 kcal/mol) colchicine site tubulin, forming key hydrophobic hydrogen bonding interactions enhance its activity. ADMET analysis confirmed favorable drug-like properties, establishing these promising candidates further development agents targeting

Language: Английский

Design, synthesis, in silico studies, and apoptotic antiproliferative activity of novel thiazole-2-acetamide derivatives as tubulin polymerization inhibitors DOI Creative Commons

Lamya H. Al-Wahaibi,

Ali M. Elshamsy,

Taha F. S. Ali

et al.

Frontiers in Chemistry, Journal Year: 2025, Volume and Issue: 13

Published: April 16, 2025

Tubulin polymerization inhibitors have emerged as interesting anticancer therapies. We present the design, synthesis, and structural elucidation of novel thiazole-based derivatives to identify tubulin with potent antiproliferative efficacy strong inhibition polymerization. The compounds consist two scaffolds. Scaffold A 10a-e scaffold B 13a-e. structures newly synthesized 13a-e were validated using 1H NMR, 13C elemental analysis. most effective antitubulin derivative was 10a, exhibiting an IC50 value 2.69 μM. Subsequently, 10o 13d exhibited values 3.62 μM 3.68 μM, respectively. These more potency than reference combretastatin A-4, which displayed 8.33 had no cytotoxic effects on normal cells, preserving over 85% cell viability at 50 experiment demonstrated that 10o, significant activity against four cancer lines, average GI50 6, 7, 8 equivalent reference's doxorubicin sorafenib. Compounds activate caspases 3, 9, Bax, while down-regulating anti-apoptotic protein Bcl2. Molecular docking studies superior binding affinities for 10a (-7.3 kcal/mol) colchicine site tubulin, forming key hydrophobic hydrogen bonding interactions enhance its activity. ADMET analysis confirmed favorable drug-like properties, establishing these promising candidates further development agents targeting

Language: Английский

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