Environmentally benign synthesis, characterization, and in vitro anticancer and anti-TB activity of indolizines, along with anti-TB and anticancer docking studies

Background The escalating prevalence of drug-resistant tuberculosis and cancer, coupled with the limitations of current therapeutics, underscores the urgent need for novel multi-target molecular scaffolds. Methods In the present study, a series of novel indolizine derivatives ( 4a–f ) was synthesized employing an environmentally benign approach designed to mitigate environmental waste and reduce economic costs while enhancing reaction efficiency and product stability. Reaction progress was monitored by thin-layer chromatography, and the products were purified by column chromatography. The molecular structures of all synthesized compounds were unequivocally confirmed by comprehensive spectroscopic analysis using FT-IR, HRMS, ¹H NMR, and ¹ ³C NMR techniques. Molecular docking studies were performed using the Schrödinger Maestro interface against four tuberculosis-associated target proteins (PDB: 4R9R, 7WVZ, 1ZVW, 6J2V) and four cancer-associated protein targets (PDB: 3D3P, 6Z4B, 5EW3, 1M17), wherein the compounds exhibited excellent hydrogen bonding interactions and favourable docking scores. The in vitro anticancer activity of the synthesized derivatives was evaluated against the A549 lung carcinoma cell line using the MTT assay. Results Compounds 4d (IC₅₀ = 9.09 µM), 4b (IC₅₀ = 15.27 µM), and 4a (IC₅₀ = 23.89 µM) demonstrated cytotoxic activity approaching that of the reference standard doxorubicin (IC₅₀ = 8.73 µM), thereby validating the molecular docking results against the cancer target protein (PDB: 1M17). Parallel anti-tubercular evaluation against Mycobacterium tuberculosis H37Rv revealed that compounds 4a , 4b , and 4c possessed potent inhibitory activity at low minimum inhibitory concentration values, while exhibiting minimal cytotoxicity against normal Vero cells, confirming the molecular docking outcomes against the InhA target (PDB: 4R9R). Conclusion Collectively, the integration of green synthetic protocols, thorough structural characterization, multi-target docking simulations, and in vitro biological evaluation positions these indolizine derivatives as promising dual-functional scaffolds for both antitubercular and anticancer drug discovery, warranting further pharmacological investigation.