Anti-tubercular agents from Ammannia baccifera (Linn.)

Abstract

Ammannia baccifera is an important component of various traditional Chinese herbal formulations. The samples of A. baccifera were extracted with methanol and the methanolic extract was successively fractionated with n-hexane, chloroform and n-butanol. The serial chromatographic separation of chloroform and n-butanol fractions resulted in the isolation and characterization of betulinic acid (1), 4-hydroxy-α-tetralone (2), tetralone-4-O-β-d-glucopyranoside (3) and ellagic acid (4). Further, the compound 2 was chemically modified into its five semi-synthetic acyl and aryl derivatives (2A–2E) namely; 4-O-m-anisoyl-α-tetralone (2A), 4-O-benzoyl-α-tetralone (2B), 4-O-palmitoyl-α-tetralone (2C), 4-O-(3,4,5-trimethoxybenzoyl)-α-tetralone (2D) and 4-O-myricitoyl-α-tetralone (2E). The tetralone group compounds 2, 3 and semi-synthetic derivatives 2A–2E were evaluated for their in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv by BACTEC-460 radiometric susceptibility assay. The compounds 2 and 2E have shown significant anti-tubercular activity (MIC 50 μg/ml) while 2B was moderate active (MIC 100 μg/ml) against the pathogen. The results of SAR study indicated that substitutions in alpha hydroxyl group of 4-hydroxy-α-tetralone either retards or have no increasement in in vitro anti-tubercular potential.