Synthesis studies, microbial evaluation and molecular docking of bis-diazoles derivatives of succinic acid.

Abstract

Five bis-diazole derivatives-specifically 1,2-bis(1,3,4-oxadiazole-2(3H)-thione-5-yl)ethane (6), 1,2-bis(4-amino-3-mercapto-4H-1,2,4-triazole-5-yl)ethane (7), 1,2-bis(3-mercapto-4H-1,2,4-triazole-5-yl)ethane (8), 1,2-bis(2-amino-1,3,4-thiadiazole-5-yl)ethane (9), and 1,2-bis(2-mercapto-1,3,4-thiadiazole-5-yl)ethane (10)-were synthesised using succinic acid as the precursor. The chemical structures of both the synthetic intermediates and the final compounds were elucidated through a combination of physicochemical characterisation and spectroscopic analysis. Furthermore, the synthesised compounds were evaluated for their antibacterial and antifungal activities, alongside their synergistic effects against a range of reference bacterial and fungal strains. In vitro antimicrobial assays were conducted against a panel of Gram-positive strains, including Staphylococcus aureus (ATCC 25923) and Enterococcus faecalis (ATCC 29212), as well as Gram-negative bacteria, such as Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). Ampicillin and gentamicin served as the reference antibiotic standards. Furthermore, the synthesised derivatives were screened against yeast strains, specifically Candida albicans (ATCC 71440), C. tropicalis (ATCC 71460), and C. parapsilosis (ATCC 71471), in addition to filamentous fungi including Aspergillus niger, A. flavus, and Alternaria sp. Amphotericin B and ketoconazole were employed as antifungal reference standards. The majority of the synthesised compounds demonstrated significant antimicrobial and antifungal activities comparable to the reference drugs; notably, the combination of compounds 6 and 7 exhibited a synergistic effect against the Staphylococcus aureus strain. Molecular docking studies were conducted to corroborate the experimental findings. This computational approach was applied to ten bacterial and fungal proteins to elucidate the intermolecular interactions, binding affinities, and structural stability of the resulting ligand-protein complexes. Such insights facilitate the targeted application of these compounds in specific therapeutic contexts.