Abstract

Structural modification of natural products is a key strategy in drug discovery. In this work, a series of camphor derivatives were synthesized by incorporating heteroaromatic aldehydes, and their anticancer and antioxidant potential was evaluated through an integrated in vitro and in silico approach. The results highlighted the thiophene 5 and benzofuran 9 derivatives as the most potent agents, exhibiting high selective cytotoxicity against gastric, colon, and prostate cancer cell lines, with IC50 values as low as 31.8 μM and a selectivity index of 7.0. The cytotoxic mechanism was found to be mediated by apoptosis induction via the mitochondrial pathway. Moreover, these active compounds displayed a favorable safety profile, showing low hemolytic activity and low predicted toxicological risk according to computational models. Overall, these findings demonstrate that camphor functionalization with specific heterocycles represents an effective strategy for developing novel anticancer drug candidates with high selectivity and a promising safety profile.