Synthesis and Antimicrobial Evaluation of Novel 1,5-Benzothiazepine Derivatives

Abstract

1,5-Benzothiazepine is an important heterocyclic ring containing benzene ring fused with a seven- membered thiazepine. This ring structure is not only found in a variety of medicinally important therapeutic agents but also enjoy a broad spectrum of bioactivities. Considering its broad bioactivities, in the present work we synthesized novel 1,5-benzothiazepine derivatives by the reaction of isobutyl chalcones with 2-aminothiophenol. The characterization of the compounds was done by physicochemical and spectral analysis (FT-IR, 1H NMR, 13C NMR and MS) and evaluated for their antibacterial and antifungal activities. The compounds with halogen atom showed very promising activity when compared to the commercial drugs, ciprofloxacin and fluconazole. Among the halogens, fluorinated compounds i.e., BT6 exhibited superior antimicrobial activity than the standard drugs with MIC 0.4 µg/mL against all the strains whereas it is active on Escherichia coli at the MIC 0.8 µg/mL. The other fluorinated compound BT5 was the most active compound against Escherichia coli with the MIC 0.4 µg/mL. BT3 with two chlorine atoms shown potent activity with MIC 0.4 µg/mL and 1.6 µg/mL against Staphylococcus aureus and Candida albicans respectively. BT5 was also more active than the standard drugs against Staphylococcus aureus, Proteus vulgaris and Aspergillus niger (MIC 0.8 µg/mL) and Candida tropicalis (1.6 µg/mL). Atom-based 3D-QSAR was carried out using the PHASE module of Schrodinger software to assess the validity of the invitro antimicrobial data. The computational studies were more or less in close harmony with the invitro activity data. The invitro biological activity data and the insilico atom-based 3D-QSAR results provide a set of guiding principles for the designing of compounds with better antibacterial and antifungal properties.