In Vitro and In Vivo Biological Evaluation of Novel 1,4-Naphthoquinone Derivatives as Potential Anticancer Agents

Abstract

A novel library of naphthoquinone derivatives (3–5aa) was synthesized and evaluated for their anticancer properties. Specifically, compounds 5i, 5l, 5o, 5q, 5r, 5s, 5t, and 5v demonstrated superior cytotoxic activity against the cancer cell lines that were studied. Notably, compound 5v displayed a greater cytotoxic effect on MCF-7 cells compared to the standard drug doxorubicin. To further investigate the mechanism of cytotoxic effect, additional anticancer studies were conducted with 5v in MCF-7 cells. The findings showed that 5v triggered cytotoxic effects in MCF-7 cells through the initiation of cell cycle arrest at the G1/S phase and necrosis. In vivo ecotoxicity studies indicated that 5v had lower toxicity towards zebrafish larvae (LC50 = 50.15 μM) and had an insignificant impact on cardiac functions. In vivo xenotransplantation of MCF-7 cells in zebrafish larvae demonstrated a significant reduction in tumour volume in the xenograft. Approximately 95% of the zebrafish larvae with 5v xenografts survived after 10 days of the treatment. Finally, a computational modelling study was conducted on four protein receptors, namely ER, EFGR, BRCA1, and VEFGR2. The findings highlight the importance of the aminonaphthoquinone moiety, amide linkage, and propyl thio moiety in enhancing the anticancer properties.