An efficient and facile green synthesis of bisindole methanes as potential Mtb FtsZ inhibitors

Abstract

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.

Advances in Key Drug Target Identification and New Drug Development for Tuberculosis

“…Several ftsZ inhibitors have been found to be effective against Mtb, including natural products containing curcumin, coumarins, berberine, and resveratrol, small-molecule compounds comprising bisindole methane derivatives, benzamides, taxanes, and rhodamine derivatives, and some polypeptides and nucleic acids [107][108][109][110]. Most of these compounds have been tested in vitro.…”

Disaggregation-induced resurgence of quenched emission of a self-assembled bis-indole system: photophysics, energetics, and dynamics

“…Studies on the biological and pharmacological activities of bis(indolyl)methanes (BIMs) have gained significant interest. [29][30][31] However, there is a lack of interest in their photophysical, dynamical, and thermodynamic properties under different conditions. We considered the spectroscopic and photophysical parameters along with the thermodynamic data for this molecular system in this biomimetic microheterogeneous media to be very helpful in developing a better understanding of the nature of binding, and also in assessing the biodistribution of this dye system within various bioenvironments.…”