Pharmacophore based approach to screen and evaluate novel Mycobacterium cell division inhibitors targeting FtsZ - A modelling and experimental study.

This study employs the use of pharmacophore models derived from two different datasets based on Mtb-FtsZ GTPase inhibition and whole cell antibacterial activity, to virtually screen and shortlist novel compounds from In-house small molecule library as Mtb-FtsZ inhibitors and evaluate their in-vitro and ex-vivo activity. The results revealed Piperine (IC50 = 21.2 ± 0.7 μM), 4-Bromo di-methoxy coumarin (IC50 = 13.0 ± 1.6 μM) and Di-ethyl amino methyl coumarin (IC50 = 19.4 ± 1.1) as potent Mtb-FtsZ GTPase inhibitors which showed considerable antibacterial activity (84.0 ± 2.6 μM, 56.0 ± 4.3 μM and 108 ± 7.1 μM respectively) against M. smegmatis. They appear to be bacteriostatic, as well as treatment these compounds lead to a 3× increase in cell length of M. smegmatis. Further these molecules also altered the FtsZ gene expression by 3-fold compared to untreated. In addition compound Aloin, an Aloe exudate showed potent Mtb-FtsZ inhibition (IC50 = 16.7 ± 0.4 μM) but exhibited poor anti-mycobacterial activity (>500 μM).
PMID: 31034983 [PubMed - as supplied by publisher]

Source: European Journal of Pharmaceutical Sciences - April 25, 2019 Category: Drugs & Pharmacology Authors: Mitra K, Chadha A, Doble M Tags: Eur J Pharm Sci Source Type: research