Metal Complexes of Curcumin: A Comprehensive Approach to Design, Synthesis, Characterization and Assessment of Anti-tubercular Activity

Background The primary challenge facing Tuberculosis (TB) is the growing prevalence of drug resistance and the hepatotoxicity secondary effects of first and second-line anti-TB treatments have reignited interest in exploring new metal drug complexes as possible sources of anti-TB medications. Aim To perform in silico studies for Curcumin-metal complexes, synthesis and evaluate their antitubercular activity and cytotoxicity. Materials and Methods Designed metal complexes were docked against 2NSD and performed ADMET studies. Based on binding affinity, a series of Curcumin-metal complexes were synthesized, characterized by IR, NMR, MASS, P-XRD and the antitubercular activity was evaluated by MABA and MTT assay for cytotoxicity investigations. Results and Discussion The binding energies ranged from -8.0 to -10.1 ‘kcal/mol’. At -10.1 ‘kcal/ mol’, the Curcumin-Cu complex (C1) exhibited the best binding. The synthesized compounds was evaluated against Mycobacterium tuberculosis (H37Rv) using the MABA assay. Curcumin-Cu complex (C1) showed the highest activity and was the most sensitive at 0.8 µg/mL and showed less toxicity with an IC50 of 10.0 and a selectivity index of 4.0. Cytotoxicity was evaluated by the ATCC CCL-81 cell line. Conclusion Therefore, we can conclude that the molecular hit will be a good lead to develop novel therapies for tuberculosis treatment.