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An efficient and facile green synthesis of bisindole methanes as potential Mtb FtsZ inhibitors
Author(s) -
Khadkikar Pratima,
Goud N. Sridhar,
Mohammed Arifuddin,
Ramamoorthy Gayathri,
Ananthathatmula Ragamanvitha,
Doble Mukesh,
Rizvi Arshad,
Banerjee Sharmista,
Ravi Alvala,
Alvala Mallika
Publication year - 2018
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/cbdd.13363
Subject(s) - ftsz , gtpase , tubulin , mycobacterium tuberculosis , bacillus subtilis , mycobacterium smegmatis , chemistry , drug discovery , small molecule , biochemistry , biology , cell division , bacteria , cell , microbiology and biotechnology , microtubule , tuberculosis , medicine , genetics , pathology
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 Mtb FtsZ 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 Mtb FtsZ 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 Mtb FtsZ 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.