Antiproliferative, DNA cleavage, and ADMET study of substituted 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid and its esters

Synthesis, anti-proliferative, DNA cleavage, and in silico ADMET studies of 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acids and their resultant esters in acid catalyzed medium have been investigated. The synthesized compounds are characterized by UV, IR, 1 H NMR, 13 C NMR, and mass spectral analysis. The electrophoretic DNA cleavage studies on λ-DNA (Eco-RI/Hinda-III double digest) using agarose gel method and the antiproliferative activity was carried out by MTT assay on five different human cancer cell lines (Chronic Myelogenous Leukemia (K562), Breast Cancer (MCF-7), Cervical Cancer (HeLa), Colorectal Adino carcinoma (Colo 205), and Hepato cellular carcinoma (HepG2)). Doxorubicin is taken as standard for comparison. The cleavage study indicated that molecules (3b-6a and 7b-8c) did cleave the DNA completely with no trace of fragments. The molecules (6b, 6c and 7a) have appeared to cleave DNA partially and assessed by comparing the bands appeared in control and test compounds at 100 μg concentration. The MTT antiproliferative activity of the synthesized derivatives at a concentration of 10 mM screened that out of the five cancer cell lines tested, the compounds 8b (25.97%, MCF-7), 7a (25.36%, Colo 205), and 7b (24.22%, HePG) showed considerable degree of activity at a very low concentration. The molecules were active against MCF-7, Colo 205, and HepG. The molecules exhibited acceptable range in in silico ADMET prediction, significant DNA cleavage, and antiproliferative properties. The study further provides identification of possible lead moiety as an antiproliferative agent.