Design and Synthesis of Propargyloxy Functionalized Pyrazole‐Based Aurones: Exploring Their Potent Anticancer Properties Against AGS and MCF‐7 Cell Lines

Abstract

FDA‐approved numerous commercial and natural drugs used in cancer treatment feature either pyrazole or alkyne moieties. Based on this, we designed and synthesized twenty novel propargyloxy‐substituted pyrazole‐based aurones (10a‐j and 11a‐j) and evaluated for their anticancer potential against cancerous MCF‐7 and AGS cell lines, as well as normal cell line HEK‐293, through MTT assay. Among these tested compounds, five (10d‐f, 11e, and 11f) displayed potent cytotoxic properties for AGS cancer cell line with IC50 values ranging from 19.7 µM ‐ 28.5 µM, better than the reference drugs Leucovorin (IC50 = 30.8 µM) and Oxaliplatin (IC50 = 29.8 µM). Furthermore, compounds 10b, 10c 11a, 11c, and 11d demonstrated a significant cytotoxic potential against the MCF‐7 cancer cell line with a single‐digit micromolar IC50 potency (4.8 µM – 8.5 µM) compared to the standard drug Paclitaxel (IC50 = 19.7 µM). The cytotoxic studies of above selected potent active hybrid compounds, against HEK‐293 (human embryonic kidney 293), normal cell line, further highlight the potential use of 10c molecule (IC50 = 4.8 μM against MCF‐7 cells) as an anti‐cancer agent for breast cancer with a selectivity index of 2.597. The cytotoxic results were further supported by the molecular docking studies.