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

FDA-approved numerous commercial and natural drugs used in cancer treatment feature either pyrazole or alkyne moieties. On the basis of this, we designed and synthesized 20 novel propargyloxy-substituted pyrazole-based aurones (10a–j and 11a–j) and evaluated for their anticancer potential against cancerous MCF-7 and human gastric adenocarcinoma (AGS) cell lines, as well as normal cell line human embryonic kidney 293 (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 to 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 (4.8–8.5 µM) compared to the standard drug paclitaxel (IC₅₀ = 19.7 µM). The cytotoxic studies of above selected potent active hybrid compounds, against HEK-293, normal cell line, further highlight the potential use of 10c molecule (IC₅₀ = 4.8 µM against MCF-7 cells) as an anticancer agent for breast cancer with a selectivity index of 2.597. The cytotoxic results were further supported by the molecular docking studies.