Abstract
In the current medical era, human health is confronted with various challenges, with cancer being a prominent concern. Therefore, enhancing the therapeutic arsenal for cancer with a constant influx of novel molecules that selectively target tumor cells while displaying minimal toxicity toward normal cells is imperative. This study delves into the antiproliferative and EGFR kinase inhibitory activities of newly reported spirooxindole-pyrazolo[3,4-b]pyridine derivatives 8a-h and 10a-h. The inhibitory effects on the growth of human cancer cell lines A-549 (lung carcinoma), Panc-1 (pancreatic carcinoma), and A-431 (skin epidermoid carcinoma) were evaluated, and the SAR has been clarified through analysis. With IC50 values in the single-digit micromolar range, compounds 8b, 8d, 10a-b, and 10d were shown to be the most effective antiproliferative candidates against the studied cancer cell lines. They also exerted negligible cytotoxicity (with selectivity scores between 8.63 and 30.02) against the human lung MRC5 cell line. Additionally, we investigated the potential inhibitory action of compounds 8b, 8d, 10a-b, and 10d on EGFR and VEGFR-2. 10a was this investigation’s most effective EGFR inhibitor, with an IC50 value of 0.54 μM. Ultimately, the molecular docking analysis of congener 10a highlighted its effective suppression of EGFR by examining its binding mode and docking score compared to Erlotinib. These findings underscore the potential of spirooxindole-pyrazolo[3,4-b]pyridine derivatives as promising anticancer agents targeting EGFR kinase.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
