Green synthesis of novel amino acid-coupled 1, 2, 4-triazoles derivatives using lemon juice as a green catalyst: Potential antiproliferative, antimicrobial, DFT computation and molecular docking analysis

Novel triazole amino acid derivatives (BTPC, CTPC, and NTPC) were synthesized in one-pot reactions and characterized with NMR, UV-Vis, and FT-IR spectroscopy. The synthesized compound chemical structure was optimized using the Density Functional Theory (DFT) B3LYP/6-311++G(d,p) basis set. The Multiwfn program was employed for topological studies such as ELF, LOL, ALIE, RDG, and ALIE (reactive sites of non-covalent interactions). The NBO analysis reveals inter and intra-molecular bond properties. The compounds' antiproliferative activity was tested against MCF-7 and HepG2 human cancer cell lines using the MTT assay. Among the compounds evaluated, NTPC demonstrated the lowest IC₅₀ values for both MCF-7 (4.92 ± 0.78 μM) and HepG2 (6.84 ± 0.81 μM) cell lines, signifying the most cytotoxic effectiveness. The antibacterial properties of the BTPC, CTPC, and NTPC compounds were tested against B. subtilis, S. aureus, E. coli, and P. aeruginosa. NTPC demonstrated the most significant antibacterial activity, with inhibition zones of 23.9 mm against S.aureus and 22.1 mm against B.subtilis. Molecular docking studies confirmed that BTPC has a higher binding affinity for both the breast cancer-associated estrogen receptor (PDB ID: 3ERT) and the liver cancer-associated EGFR kinase (PDB ID: 5UGB) than the other tested compounds CTPC, NTPC, and the reference drugs fluorouracil and sorafenib.