Molecular modelling, cytotoxicity & biological investigation of novel fluorinated diphenylamine chalcone derivatives

Abstract

A unique series of 1-(3-(3,4-difluorophenyl)amino)phenyl)ethan-1-one linked fluorinated diphenylamine chalcones (A1-A7) were synthesized and characterized by NMR, IR, and MS. The compounds were studied in vitro for antibacterial and antifungal activities. In vitro studies show that the compound had significant antibacterial (MICs 25–250 µg/ml) and antifungal (MICs 250–1000 µg/ml) properties. Chemicals A1, A2, and A4 significantly inhibited all bacterial strains, whereas compounds A1, A4, and A7 inhibited fungal very marginally. Compounds A1 and A2 had a high anti-Plasmodium falciparum activity. A molecular docking investigation discovered that compounds A1 and A2 significantly bind to the active site of falcilysin. Compound A1 maintains its stability through numerous van der Waals interactions with falcilysin protein residues. Compound A2, on the other hand, shows a hydrogen bond with Asn421, the secondary amine linked to the phenyl ring. The Molecular Dynamic simulation at 100 ns to investigate the dynamic stability of protein-ligand complexes. Compounds A1 and A2 exhibited the highest binding affinity and interaction. According to the MD simulation results, the proposed drug maintains the molecular interaction and structural integrity with P. falciparum. In HeLa cells, the cytotoxicity of compounds A1 and A4 was examined. A1 and A4 had computed LC50 values of 19.14 µg and 21.01 µg, respectively. Both compounds are cytotoxic to HeLa cells, according to the observations above. Compounds A1 and A2 are potential lead compounds for novel drug-like molecules having antibacterial, antifungal, and antimalarial properties.