Abstract
Background: The antibacterial, antifungal and antiparasitic activities of some novel benzosultams and benzosultones in vitro systems are tested. The antibacterial activity has been tested against gram negative bacterium Escherichia coli (E. coli) and gram positive Bacillus subtilis (B. subtilis). The antifungal activity has been tested against an opportunistic pathogenic fungal strain namely Pichia guilliermondii SNP3S. The antiparasitic activity has been tested against filarial parasite Setaria cervi. The active compound 4,7-dimethyl-3,4,7,8-tetrahydro-3λ6-[1,2]thiazino[4,3-f]quinoline-3,3,8-trione was found to exert no toxicity when tested on rat peritoneal macrophage culture. The compounds show moderate to excellent biological activities. The molecular modeling has also been done to compare their inhibitory affinity on human matrix metalloproteinase 9 (MMP-9).
Methods: The compounds were initially dissolved in DMSO (Merck, Germany) for making stock thereafter diluted in RPMI dissolved in Milli-Q water to yield desired concentrations (20-100 µg/ml) and used in the study. The commercially available antibacterial and antifungal antibiotics namely Ciprofloxacin and Fluconazole were dissolved in Milli-Q water whereas standard filaricide Ivermectin was prepared in DMSO. Before applying to the biological system, the solution of each compound was filtered through 0.22 µm membrane filters (Millipore, USA). Results: Among the tested ones, compound 8l was found highly active (inhibition zone: 20.5 mm for E. coli and 19 mm for B. subtilis) against the two different types of bacteria tested. In other side, compound 8a-d, 8h and 8i were found to exert some degree of antibacterial effect termed as moderately active. However, compound 8e, 8f and 8k were found to exert no effect on any of the microbes. Conclusion: In this study, we have tested the bioactivity of twelve synthesized compounds at a low dose (50 µg/ml) whereas cytotoxicity was tested at much higher dose (200 µg/ml). The main focus behind the bioactivity and cytotoxicity study was to screen a compound that serve as highly bioactive with low toxicity. Sultam 8l was found to exert minute cytotoxicity in rat peritoneal macrophage culture up to 200 µg/ml which is four times higher than its minimum inhibitory concentration (MIC) for antiparasitic (50 µg/ml) and twenty times than antimicrobial activity (10 µg/ml). Therefore, the active compound 8l may be considered as a possible therapeutic. The molecular modeling of these compounds reveals that they have significant and comparable inhibition affinity towards MMP-9 due to their negative electrostatic potential.Keywords: Antibacterial, antifungal, antiparasitic, benzosultams, benzosultones, molecular modeling, binding affinity.
Graphical Abstract
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