Synthesis, antitumor activity evaluation, and DNA ‐binding study of coumarin‐based agents

Abstract A novel series of coumarin‐thiadiazole heterocycle derivatives was synthesized by the nucleophilic substitution reaction. The synthesized compounds were structurally verified by IR, 1H NMR, 13C NMR, mass spectra, and elemental analyses. The antitumor activity of the synthesized compounds was evaluated through DNA binding assays and the 60‐cell line panel according to the US NCI‐DTP protocol or a selection of human tumor cell lines: breast cancer (MCF‐7), liver cancer (HepG‐2), and colorectal cancer (HCT‐116). Most of the compounds had better DNA/ethidium bromide fluorescence quenching rather than methyl green displacement, suggesting superior DNA intercalation over DNA groove binding. Compounds 8 and 14b showed the best quenching effect with KSV = 4.27 × 105 M−1. Moreover, the results for compounds 8, 4c, and 4e revealed a possible dual DNA binding mode with the intercalation to be superior, with KSV 4.27 × 105, 3.96 × 105, and 3.51 × 105 M−1, respectively, compared to 42%, 45%, and 43% methyl green displacement, respectively. Out of the 60‐cell line panel, the leukemia HL‐60 cell line was the most susceptible to growth inhibition when treated with 14a, resulting in 61% growth, followed by the lung carcinoma cell line NCI‐H522 showing 67% growth when treated with 9. Moreover, compound 10c had an IC50 value of 24.9 μg/mL against the HepG‐2 cell line. Novel coumarin‐thiadiazole heterocycle derivatives were evalu...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: FULL PAPER Source Type: research