Current scenario of indole-azole hybrids with anticancer potential: part I. triazole and pyrazole hybrids.

Cancer therapy is still hampered by key challenges, including drug resistance, poor target selectivity, and narrow therapeutic spectra, driving the pursuit of novel anticancer agents with enhanced efficacy and safety. Indole-triazole/pyrazole hybrids, formed by fusing indole scaffolds with triazole/pyrazole, confer inherent structural diversity and high modifiability. Structurally, rational modification of indole/triazole/pyrazole moieties allows optimization of pharmacokinetic properties and improves cancer cell selectivity, minimizing toxicity to normal cells. Functionally, indole-triazole/pyrazole hybrids exhibit multitargeted activity to simultaneously inhibit key oncogenic pathways, addressing the heterogeneity of cancer pathogenesis, while their hybrid structure enhances anticancer potency. This multitargeted mode also aids in overcoming drug resistance, a major bottleneck in clinical therapy. Accordingly, indole-triazole/pyrazole hybrids have emerged as a promising class of anticancer candidates. This review summarizes recent advances in indole-triazole/pyrazole hybrids with anticancer potential, covering articles published from 2021 to the present. To delineate the key molecular features governing anticancer potency, this review further presents a detailed analysis of structure-activity relationships (SARs) and conducts an in-depth exploration of the underlying mechanisms of action.