Antiproliferative and apoptotic activity of new indazole derivatives as potential anticancer agents

Abstract

To develop potent and selective anticancer agents, a series of novel polysubstituted indazoles was synthesized and evaluated for their in vitro antiproliferative and apoptotic activities against two selected human cancer cell lines (A2780 and A549). Several compounds showed an interesting antiproliferative activity, with IC 50 values ranging from 0.64 to 17 µM against both cell lines. The most active indazoles were then tested in different pharmacological dilution conditions, adding five new cell lines (A2780, A549, IMR32, MDA-MB-231, and T47D) as targets, confirming their antiproliferative activity. Furthermore, selected compounds were able to trigger apoptosis to a significant extent and to cause, in part, a block of cells in the S phase of the cell cycle, with a concomitant decrease of cells in the G2/M and/or G0/G1 phases and the generation of hypodiploid peaks. However, molecule 7d caused a great increase of cells in G2/M and the appearance of polyploid cells. Altogether, our results suggest a good pharmacological activity for our selected polysubstituted indazoles, which are suggestive of a preferential mechanism of action as cell cycle-specific antimetabolites or as an inhibitor of enzyme activities involved in DNA synthesis, except for 7d, which, on the contrary, seems to have a mechanism involving the microtubule system.

“Synergistic Innovation: Crafting Indazole Derivatives for Advanced Anticancer, Antioxidant, and Antimicrobial Efficacy through Integrative Design and Holistic Evaluation”

“…This adaptability empowers researchers to intricately fine-tune the characteristics of indazole derivatives, augmenting their precision and efficacy against cancer cells while minimizing any unintended impacts on healthy tissues. [41,42] Concerns regarding resistance to antimicrobial agents have become a global issue, fueling an ongoing battle between humans and bacteria that significantly impacts global wellbeing. Current estimates indicate that microbial infections contribute to approximately 0.7 million deaths annually, a number that continues to rise.…”

“…Notably, the molecular framework of indazole lends itself to facile structural adjustments, providing a versatile foundation for tailoring targeted therapeutics (refer to Figure 2). This adaptability empowers researchers to intricately fine‐tune the characteristics of indazole derivatives, augmenting their precision and efficacy against cancer cells while minimizing any unintended impacts on healthy tissues [41,42] …”