Zinc chloride-catalyzed synthesis of indole-based α-aminophosphonates with potent antimicrobial and anticancer activities: <i>in vitro</i> and <i>in silico</i> evaluation

AIM: This study aimed to synthesize new α-aminophosphonate derivatives based on 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde and evaluate their anticancer, antimicrobial, and drug-likeness properties supported by molecular docking studies. MATERIALS & METHODS: )-catalyzed reaction. The synthesized compounds were characterized by standard spectroscopic techniques. Antiproliferative activity was evaluated using MTT assays against MCF7 and HepG2 cancer cell lines. Antimicrobial activity was assessed against Gram-positive and Gram-negative bacteria and fungi. Molecular docking and ADMET analyses were also performed. RESULTS: values of 9.5 and 9.2 µM, comparable to doxorubicin (9.4 µM). All compounds demonstrated lower cytotoxicity toward HepG2 cells. Compound 5d showed the strongest antimicrobial activity with MIC values of 10-20 µg/mL, surpassing gentamicin. Molecular docking has revealed key hydrogen-bonding and π-interactions supporting dual biological activities. ADMET profiling indicated favorable drug-like properties for compounds 5a-5e. CONCLUSION: The synthesized α-aminophosphonates represent promising candidates for future development as dual anticancer and antimicrobial agents.