In Silico Molecular Docking and Synthetic Elaboration of New Phthalazine Scaffolds Functionalized with a Phthalyl Moiety for Putative Antimicrobial Potency

This study investigated the synthesis and evaluation of novel phthalazine derivatives bearing phthalyl amino acid moieties as potential antibacterial and antifungal agents . A series of phthalazine derivatives (3 a-g ) were synthesized by condensing phthalazin -1(2H) – one with various phthalyl amino acids ( glutamine , methionine , tyrosine , histidine , alanine , phenylalanine and glycine ) using N,N՝- dicyclohexylcarbodiimide (DCC) as a dehydrating agent . Subsequent removal of the phthalyl protecting group yielded the corresponding free amino acid derivatives (4 a-g ) The bioactivity of the synthesized compounds was scrutinized for antimicrobial efficacy, with certain candidates exhibiting auspicious potential. Computational molecular docking analyses were executed to decipher the intricate binding affinities and interaction dynamics between the synthesized compounds and their respective targets and their putative targets, revealing a correlation between binding affinity and antibacterial activity. The molecular architectures of the synthesized compounds were unequivocally authenticated through advanced spectroscopic modalities, including ¹H-NMR, mass spectrometry, and infrared (IR) spectroscopy, alongside comprehensive elemental composition analysis.