Abstract

The persistent global health challenge posed by the emergent spread of drug-resistant Mycobacterium tuberculosis (Mtb) has created an urgent need to identify antitubercular agents with novel mechanisms of action that can be used in combination with established antitubercular drugs. The objective of this research was to assess the antitubercular potential of phytochemical components of Datura innoxia Mill. (downy thorn-apple) against Mtb using in vitro and in silico methods. Bioassay-guided fractionation and LC-MS/MS analysis were used for the identification of secondary metabolites with anti-tuberculosis activity in methanolic leaf extracts of D. innoxia. The strongest antitubercular activity was exhibited by trans-3-indoleacrylic acid with a minimum inhibitory concentration (MIC) of 3.12 μg/mL and minimum bactericidal concentration (MBC) of 12.5 μg/mL. Screening structural analogs of trans-3-indoleacrylic acid for antitubercular activity identified several analogs (indole-3-propionic acid, indole-3-acetonitrile and 3-(1-naphthyl)acrylic acid) with lower antitubercular activity than trans-3-indoleacrylic acid.  The study of leaf extracts of D. innoxia also identified additional components with substantial antitubercular activity.  One active component was o-vanillin, which exhibited an MIC of 12.5 μg/mL, and an MBC of 50 μg/mL.  Another active component was 4-n-pentylaniline, which exhibited a MIC of 25 μg/mL, and an MBC of 200 μg/mL. These D. innoxia components are candidates for additional structure-activity relationship studies aiming to identify substances having increased antitubercular potency while maintaining favorable stability and toxicity profiles.