期刊
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
卷 37, 期 1, 页码 1903-1917出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/14756366.2022.2085693
关键词
Apoptosis; anticancer; VEGFR-2 inhibitors; 2-Oxo-1; 2-dihydroquinoline; Thiazolidine-2; 4-dione; 2-Oxoindoline
资金
- Princess Nourah bint Abdulrahman University Researchers Supporting Project, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia [PNURSP2022R116]
- Research Center at AlMaarefa University
In this study, a thiazolidine-2,4-dione nucleus was combined with effective antitumor moieties to create new hybrids with potential activity against VEGFR-2. Compound 12a showed the strongest inhibitory effect on various cancer cell lines and exhibited high affinity for VEGFR-2. Furthermore, all tested compounds demonstrated high safety profiles in non-cancerous cell lines.
A thiazolidine-2,4-dione nucleus was molecularly hybridised with the effective antitumor moieties; 2-oxo-1,2-dihydroquinoline and 2-oxoindoline to obtain new hybrids with potential activity against VEGFR-2. The cytotoxic effects of the synthesised derivatives against Caco-2, HepG-2, and MDA-MB-231 cell lines were investigated. Compound 12a was found to be the most potent candidate against the investigated cell lines with IC50 values of 2, 10, and 40 mu M, respectively. Furthermore, the synthesised derivatives were tested in vitro for their VEGFR-2 inhibitory activity showing strong inhibition. Moreover, an in vitro viability study against Vero non-cancerous cell line was investigated and the results reflected a high safety profile of all tested compounds. Compound 12a was further investigated for its apoptotic behaviour by assessing the gene expression of four genes (Bcl2, Bcl-xl, TGF, and Survivin). Molecular dynamic simulations authenticated the high affinity, accurate binding, and perfect dynamics of compound 12a against VEGFR-2.
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