In vitro investigation of Datura innoxia phytocompounds against Mycobacterium tuberculosis H37Ra strain in association with in silico studies.

Tuberculosis (TB) is a recurrent and progressive bacterial disease caused by Mycobacterium tuberculosis (Mtb), posing a significant challenge globally due to its drug resistance. This study focuses on identifying natural phytocompounds from the plant Datura innoxia (leaves), which is well known for its biologically active metabolites. Initially, the current study employed in vitro analysis of 20 phytocompounds, revealing that the natural compound 9, o-vanillin, exhibited the best minimal inhibitory concentration (MIC) which was 12.5 µg/mL, and minimal bactericidal concentration (MBC) was 50 µg/mL, all other phytocompounds showing remarkable antitubercular activity against the Mtb H37Ra strain. The molecular docking and simulation also validated the strong affinity and stable binding interactions between compound 9 and target protein kinase. The pharmacokinetic analysis highlighted the suitable oral bioavailability and no significant CYP450 inhibition for the lead compound 9, reducing the risk for drug-drug interactions. Moreover, the density functional theory analysis of lead compound 9 demonstrated optimal molecular properties, further contributing to the chemical stability and reactivity. Therefore, these results suggest that D. innoxia contains the potent phytocompound o-vanillin, which possesses antitubercular activity and can potentially be used as a drug against TB. However, future studies will focus on in vivo validation and formulation development for clinical applications.