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

Introduction 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. Methods The compounds consist two scaffolds. Scaffold A 10a-e scaffold B 13a-e . structures newly synthesized were validated using 1 H NMR, 13 C elemental analysis. Results Discussion most effective antitubulin derivative was 10a , exhibiting an IC 50 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 experiment demonstrated that significant activity against four cancer lines, average GI 6, 7, 8 equivalent reference’s doxorubicin sorafenib. Compounds 10a, 10o, activate caspases 3, 9, Bax, while down-regulating anti-apoptotic protein Bcl2. Molecular docking studies superior binding affinities for (-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 and biological evaluation of pyrrolopyrimidine urea derivatives as novel KRASG12C inhibitors for the treatment of cancer DOI

Yanguo Shang,

M. Pang,

Shengnan Fu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 289, P. 117391 - 117391

Published: Feb. 13, 2025

Language: Английский

Citations

1
Development of the Pyrido[2,3-d]pyrimidin-7(8H)-one Scaffold toward Potent and Selective NUAK1 Inhibitors DOI Creative Commons
Timothy P. C. Rooney, Gregory G. Aldred,

David Winpenny

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 25, 2025

The protein kinase NUAK1 has been implicated in various biological functions including cell adhesion, migration and proliferation. Genetic reduction of expression notably shown to lower total levels human tau a tauopathy mouse model, identifying this as potential therapeutic target for neurodegenerative disease. In paper, we describe improvement the potency, kinase-selectivity pharmacokinetic properties brain-penetrant but unselective CDK4/CDK6/NUAK1 inhibitor ON123300. Through scaffold-optimization approach have identified different chemotypes delivering inhibition with improved potency selectivity over CDK kinases compared We present ADME profiling vivo data these compounds.

Language: Английский

Citations

0
Advancing Src Kinase Inhibition: From Structural Design to Therapeutic Innovation - A Comprehensive Review DOI

Yifeng Su,

Kun Zhu,

Jiahao Wang

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117369 - 117369

Published: Feb. 4, 2025

Language: Английский

Citations

0
Effective synthesis and anti-mycobacteriuml activity of isoxazole-substituted pyrrolopyrimidine and isoxazole-substituted indole derivatives DOI

Yafei Xue,

Yongchang Bi,

Jingjun Wang

et al.

Journal of the Iranian Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: April 5, 2025

Language: Английский

Citations

0
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

Introduction 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. Methods The compounds consist two scaffolds. Scaffold A 10a-e scaffold B 13a-e . structures newly synthesized were validated using 1 H NMR, 13 C elemental analysis. Results Discussion most effective antitubulin derivative was 10a , exhibiting an IC 50 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 experiment demonstrated that significant activity against four cancer lines, average GI 6, 7, 8 equivalent reference’s doxorubicin sorafenib. Compounds 10a, 10o, activate caspases 3, 9, Bax, while down-regulating anti-apoptotic protein Bcl2. Molecular docking studies superior binding affinities for (-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

Citations

0