A series of novel 5-chloro-6-methylaurone derivatives (6a-p) were synthesized and characterized by various spectroscopic techniques. The synthesized compounds were tested for anticancer activity against 60-human cancer cell line panel derived from nine cancer types at NCI, Bethesda, USA. Among the synthesized compounds, six compounds (6e, 6f, 6h, 6i, 6k and 6 m) exhibited growth inhibition and cytotoxic activity against various human cancer cell lines in one-dose data. The most potent compound among the series, 6i was active against 55 out of 60 human cancer cell lines. Compound 6i showed remarkable % growth inhibition and cytotoxicity against various cancer cell lines exhibiting % GI in the range 36.05-199.03. The compound 6i was further evaluated for five dose assay and exhibited GI50 1.90 µM and 2.70 µM against melanoma and breast cancer cell lines respectively. Further evaluation of 6i for five-dose assay exhibited a diverse spectrum of anti-cancer activity towards all the 60 human cancer cell line panel with the selectivity index ratio ranging 0.854-1.42 and 0.66-1.35 for GI50 and TGI respectively. Based on one-dose and five-dose data compound 6i was further evaluated for cell apoptosis against MDA-MB-468 breast cancer cell line and was found to induce early apoptosis in cells explaining its mode of action. The in-silico studies for the synthesized compounds as LSD1 inhibitors (2H94) have shown better docking score and binding energy comparable to vafidemstat. All the compounds followed Lipinski rule of five. These findings concluded that the compound 6i could lead to the development of a promising therapeutic anticancer agent.
Keywords: Aurones; SYTO 9 staining; anticancer activity; cell apoptosis; molecular docking studies.