Antitumor Activity of a Quinoline-Substituted Chalcone Epoxide

Abstract

Cancer is a multifactorial disease. Chalcones have been identified as potential antitumor agents that target tubulin. This study aims to synthesize and evaluate the antitumor activity of a quinoline-substituted chalcone epoxide as a potential tubulin inhibitor. The compound was synthesized by Claisen-Schmidt condensation and named C1, its structure was established using various spectroscopic techniques. The median lethal dose (LD50) of C1 was evaluated using OECD 425 guidelines, antitumor activity was evaluated in 1-methyl nitrosourea (MNU)-induced mammary tumors in rats. Eight weeks post-MNU administration, the animals were divided into five groups of six rats each and treated with graded doses (12.5, 25, and 50 mg/kg) of C1 and paclitaxel (10 mg/kg) for six weeks. At the end of the treatment, the rats were euthanized, and mammary glands were collected and subjected to histological assessment to confirm tumor induction and assess treatment with C1. The possible mechanism of action of C1 was elucidated in silico using molecular docking. The LD50 of C1 was above 2000 mg/kg. There was significant decrease (p = 0.041) in mean tumor diameter when compared with the untreated group. Histological assessment shows that the lactiferous gland of the rats treated with MNU and graded doses of C1 showed fewer signs of hyperplasia with a small number of tumor cells in the duct when compared with the cancer control group. Tubulin-binding interaction revealed that C1 and Colchicine have the same binding site. These results suggest that C1 may have potential anticancer activity possibly via microtubule destabilization.