Insights into anti-tuberculosis activity of partially purified bioactive fraction from Vitex negundo L. petroleum ether extracts against Mycobacterium smegmatis - An in vitro and in silico approach

Abstract

The urgent need to search for new anti-TB drugs that are safer and efficient against drug resistant TB have turned towards natural medicine as they contain active ingredients capable of combating the epidemic. Medicinally important plant Vitex negundo L. has various health benefits such as anti-inflammatory, hepatoprotective activity and others. However, knowledge on exact compound(s) responsible for anti-TB activity is limited. In this study, partially purified petroleum ether extract of Vitex negundo leaves were assessed for its anti-tuberculosis and anti-biofilm activity against Mycobacterium smegmatis. Minimal inhibitory concentration of the active fraction was assessed by REMA assay (MIC > 12.5 μg/mL) and time-kill assay (67% inhibition). Anti-biofilm activity was assessed using crystal violet assay (~6.20 μg/mL). Possible compounds from the bioactive fraction were identified using FT-IR and GC-MS analysis displayed presence of classes like terpenoids, flavonoids and alkaloids. These compounds were subsequently docked against cell-wall proteins KasA, MabA, FabD and HadAB of Mtb showing HIT 3 was effective in the interaction with all targets. Molecular dynamic simulation of Hit 3 demonstrated a stable interaction with all the target proteins and can be considered as a starting point for developing new drug candidates or as an adjuvant against TB infection.