Artemisia herba-alba sesquiterpenes: in silico inhibition in the ATP-binding pocket

Abstract

To identify antimicrobial leads for medical applications, metabolites from the aerial part of Artemisia herba-alba were extracted and chromatographically purified. Two new sesquiterpenes, 1β,8α-dihydroxyeudesm-4-en-6β,7α,11βH-12,6-olide (1) and 1β,6α,8α-trihydroxy, 11α-methyl-eudesma-4(15)-en-13-propanoate (2) along with a known eudesmanolide 11-epi-artapshin (3) were identified. Structures were determined by spectroscopic methods including 1D- and 2D-NMR as well as mass spectroscopy. Compound 3 inhibited Gram-positive bacteria Bacillus subtilis, Lactobacillus cereus and Staphylococcus aureus and exhibited antifungal activity against the pathogenic fungus F. solani. The mode-of-action of these antimicrobial sesquiterpenes as bacterial type II DNA topoisomerase and/or DNA gyrase B inhibitors were examined via in silico studies. Such molecular-docking studies were also employed to examine antifungal activity against an N-myristoyl transferase (NMT) target. Compound 3 had the greatest gyrase B binding affinity in the ATP-binding pocket and was found to possess an inhibitory action against non-invasive micro-test technology (NMT).