Design, Synthesis and Biological Evaluation of Novel Gypsogenin Derivatives as Potential Anticancer and Antimicrobial Agents.

Abstract

Natural compounds are important sources for the treatment of chronic disorders such as cancer and microbial infectious disorders. In this research, Gypsogenin and its derivatives (2a-2f) have been tested against different cancer cell lines (MCF-7, HeLa, Jurkat and K562 cell lines) and further analyzed for cell proliferation, cell death type, and for act of the mechanism. Cell proliferation was determined by the MTT method and cell death types were analyzed with HO/PI staining. Fibroblast Growth Factor 1 (FGF-1), Interleukin 1 (IL-1), Interleukin 6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-α), key players in breast cancer development and progression, were determined by Elisa kits. Results showed that compound 2e inhibited the MCF-7 cell line proliferation with an IC50 value of 0.66±0.17 µM with 93.38% apoptosis rate. Compound 2e also decreased FGF-1, IL-1, IL-6, and TNF-α levels. Molecular docking studies performed in the binding site of FGFR-1 indicated that compound 2e formed key hydrogen bonding with Arg627 and Asn568. Besides, compounds 2a-2f were evaluated for their antimicrobial activities against gram-negative and gram-positive bacteria and C. albicans via the microdilution method. Overall, compound 2e stands out as a potential anticancer agent for future studies.