SYNTHESIS, CHARACTERIZATION AND EVALUATION OF QUINOLINE DERIVATIVES AS POTENT ANTITUBERCULAR AND ANTITUMOUR ACTIVITY

Abstract

Background: Tuberculosis and cancer remain major global health challenges due to drug resistance, treatment toxicity, and poor patient compliance. These limitations necessitate the development of novel dual-acting therapeutic agents with improved efficacy and safety. Objective: To synthesize, characterize, and evaluate quinoline derivatives for dual antitubercular and anticancer activities and investigate their structure–activity relationships. Methods: Twelve quinoline derivatives (QD1–QD12), including nine hydrazone/Schiff base derivatives and three Cu (II)/Zn (II) metal complexes, were synthesized by cyclization–condensation reactions (58–85% yield). The compounds were characterized by IR, ¹H/¹³C-NMR, ESI-MS, and CHN analysis. Antitubercular activity against Mycobacterium tuberculosis H37Rv was determined using the broth micro dilution method, while anticancer activity was evaluated against A549 and MCF-7 cell lines using isoniazid, rifampicin, doxorubicin, and cisplatin as reference drugs. Results: The compounds exhibited MIC values of 1.56–50.0 µg/mL. QD10 showed the highest antitubercular activity (MIC = 1.56 µg/mL; 2.3 µM) and potent anticancer activity against A549 (IC₅₀ = 9.8 µM) and MCF-7 (IC₅₀ = 7.4 µM) cells, with selectivity indices of 11.2 and 14.9, respectively. Metal complexation enhanced biological activity by 4–8-fold compared with free ligands, while electron-donating and halogen substituents further improved potency. Conclusion: QD10 emerged as the most promising dual-acting quinoline derivative, demonstrating potent antitubercular and anticancer activities with high selectivity, making it a potential lead compound for future drug development.