Microwave Synthesis, Evaluation, and Docking Study of Amino Acid Derivatives of 7-Chloroquinoline: Exploring Cytotoxic and Antioxidant Potentials

Abstract

New carbamate and amino acid derivatives of 7-chloroquinoline were synthesized and characterized using FTIR, ¹H NMR, ¹³C NMR, and HRMS analysis. The synthesized compounds were obtained through a benzotriazole-mediated approach via microwave synthesis and evaluated for antioxidant and anticancer activities. All the synthesized compounds have antioxidant properties though less than those of the standard. Cytotoxic activities of new 7-chloroquinolinyl benzyl amino carbamate derivatives were accessed using LNCaP (Lymph Node Carcinoma of the Prostate), A2780 (human ovarian cancer), and MCF-7 (breast cancer) cell lines. For cytotoxicity research, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used. The synthesized compounds were subjected to a cell viability assay, and following a 24 h treatment, the IC₅₀ values were determined. Among all the tested compounds, compound <b>4b</b> demonstrated comparable antitumor activity against LNCaP, A2780, and MCF-7 cell lines when compared to the standard drug docetaxel with IC₅₀ values of 6.61, 2.81, and 5.69 μg/mL for LNCaP, A2780, and MCF-7 cell lines, respectively. A molecular docking study targeting the β-tubulin enzyme revealed that compounds <b>4a</b>, <b>4b</b>, and <b>5b</b> exhibit a high affinity for the taxane binding site and may mimic the action of docetaxel.