Azoalkyl ether imidazo[2,1-b]benzothiazoles as potentially antimicrobial agents with novel structural skeleton |
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Authors: | Swetha Kameswari Maddili Zhen-Zhen Li Vijaya Kumar Kannekanti Rammohan R Yadav Bheemanaboina Balaraju Tuniki Vijai Kumar Reddy Tangadanchu Cheng-He Zhou |
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Institution: | Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, PR China |
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Abstract: | A series of new azoalkyl ether imidazo2,1-b]benzothiazoles were developed via a convenient synthetic procedure. The antimicrobial assays showed that a good number of the prepared derivatives exhibited significant inhibitory properties against most of the tested strains. Especially 2-methyl-5-nitroimidazole derivative 5a presented superior inhibit activity against MRSA and B. typhi with MIC?=?4?μg/mL and MIC?=?1?μg/mL, respectively. The highly active compound 5a showed low toxicity against mammalian cells without obvious triggering of the development of bacterial resistance, and it also possessed rapid bactericidal efficacy. Molecular docking study exposed that the active molecule 5a could interact with the active site of S. aureus gyrase through hydrogen bond. Quantum chemical studies were also performed to explain the high antibacterial activity. Further investigation revealed that compound 5a could significantly associate with gyrase–DNA complex by mean of hydrogen bonds and could efficiently intercalate into MRSA DNA to form 5a–DNA supramolecular complex, which impart potent bioactivity. |
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Keywords: | Antimicrobial Antifungal MRSA DNA interaction Molecular modeling |
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