Design, synthesis, in silico studies, and antiproliferative activity of a novel series of thiazole/1,2,3-triazole hybrids as apoptosis inducers and multi-kinase inhibitors endowed with anti-breast cancer activity
Fatma A. M. Mohamed, Saleha Y. M. Alakilli, Hassan H. Alhassan, Sara Osman Yousif, Eid Alatwi, Hesham A. M. Gomaa, Heba Abu Alrub, Bandar A. Alyami, Ahmed H. Abdelhafez, Stefan Bräse, Bahaa G. M. Youssif
TL;DR
Researchers developed new hybrid compounds that show strong anti-breast cancer activity by inducing cell death and inhibiting multiple cancer-related enzymes.
Contribution
A novel series of thiazole/1,2,3-triazole hybrids was developed with potent anti-breast cancer activity and multi-kinase inhibition.
Findings
Compounds 10e and 10k showed potent antiproliferative activity against MCF-7 cells with IC50 values of 24 nM and 21 nM.
Compounds 10e and 10k effectively inhibited EGFR, HER-2, and VEGFR-2 kinases with IC50 values in the low nanomolar range.
Apoptosis appears to contribute to the antiproliferative effects of the compounds based on apoptotic marker assays.
Abstract
A novel series of thiazole/1,2,3-triazole hybrids has been developed and evaluated for their in vitro anticancer efficacy. Compounds 10c, 10e, 10k, 10m, 10n, and 10o exhibited superior anticancer efficacy against the evaluated cancer cell lines, demonstrating a favorable safety profile, particularly against MCF-7 breast cancer, compared to erlotinib. The in vitro anti-breast cancer assay of compounds 10e and 10k demonstrated potent antiproliferative activity against the MCF-7 breast cancer cell line, with IC50 values of 24 nM and 21 nM, respectively, relative to the reference erlotinib, which exhibited an IC50 value of 40 nM. To elucidate their antiproliferative mechanism, tests for EGFR, HER-2, VEGFR-2, and BRAFV600E kinases were performed. Compounds 10e and 10k exhibited the highest potency as multi-EGFR/HER-2/VEGFR-2 kinase inhibitors, with IC50 values of 73 ± 4 nM (EGFR), 31 ± 2 nM…
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Taxonomy
TopicsClick Chemistry and Applications · Synthesis and biological activity · Synthesis and Reactivity of Heterocycles