An efficient and facile green synthesis of bisindole methanes as potential Mtb FtsZ inhibitors
| Autor: | Ragamanvitha Ananthathatmula, Alvala Ravi, Mallika Alvala, Sharmista Banerjee, Gayathri Ramamoorthy, N. Sridhar Goud, Arifuddin Mohammed, Pratima Khadkikar, Mukesh Doble, Arshad Rizvi |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Indoles Cell division Mycobacterium smegmatis Antitubercular Agents Microbial Sensitivity Tests Bacillus subtilis 01 natural sciences Biochemistry 03 medical and health sciences Bacterial Proteins Drug Discovery FtsZ Pharmacology Binding Sites biology Chemistry Drug discovery Organic Chemistry Green Chemistry Technology Biological activity Mycobacterium tuberculosis biology.organism_classification Protein Structure Tertiary 0104 chemical sciences Molecular Docking Simulation Cytoskeletal Proteins 010404 medicinal & biomolecular chemistry 030104 developmental biology Tubulin Docking (molecular) biology.protein Molecular Medicine Methane |
| Zdroj: | Chemical Biology & Drug Design. 92:1933-1939 |
| ISSN: | 1747-0277 |
| DOI: | 10.1111/cbdd.13363 |
| Popis: | The rising multidrug-resistant Mycobacterium tuberculosis (Mtb) strain made current anti-TB drug therapy ineffective and became a major health concern globally; hence it is crucial to develop new molecules against vital targets with a novel mechanism. Mtb Filamenting temperature sensitive protein Z (FtsZ), a tubulin homolog plays a major role in bacterial cell division, in the presence of GTP recruiting essential proteins for cell division and considered to be a potential target for drug discovery. Most of MtbFtsZ inhibitors known are of antibiotics from natural resources and suffer from cellular uptake, specificity. In the present study, we demonstrated for the first time bisindole derivatives as potential MtbFtsZ inhibitors. The synthesis of bisindole derivatives has been carried out using green synthetic approach by applying ammonium molybdate as a catalyst under Ultrasonic condition. Among the synthesized bisindole derivative, I16 and I5 showed 62.29% and 56.86% inhibition of GTPase activity of MtbFtsZ and increased the length of Mycobacterium smegmatis and Bacillus subtilis by two folds. Further compound I16 inhibited Mtb growth with a MIC of 37.5 μg/ml. To explain these interactions, detailed Molecular docking studies have been carried out and found to be supportive to the biological activity. |
| Databáze: | OpenAIRE |
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