Plant-based multi-target directed antitubercular ligand identification from Ipomea sepiaria with application of bioinformatics methodology

Abstract

Tuberculosis (TB) remains a global health threat, with approximately 10.8 million cases reported worldwide in 2023. Complexities exist in the treatment strategies for TB because of the emergence of drug resistance, necessitating research to identify novel agents from natural sources to combat this ailment. Ipomea sepiaria, a perennial herb belonging to the tropical and subtropical regions rich with phytoconstituents, has been used traditionally to treat several diseases. However, the antitubercular potential of this herb has remained elusive. Hence, plant-based multi-target directed antitubercular ligand identification from I. sepiaria was carried out by extracting phytocompounds from the leaves using petroleum ether (PE), ethyl acetate (EA), ethanol, and water as solvents. The anti-mycobacterial potential of the extracts was screened using the Mycobacterium tuberculosis, H37Rv strain by luciferase reporter phage assay. GC–MS analysis followed by in silico molecular docking studies were carried out for the PE, EA, and ethanol extracts. PE and EA extracts showed equipotent (94.35 % inhibition) and mild (45.52 % inhibition) antitubercular activity. There were 16, 14, and 15 compounds identified in the PE, EA, and ethanolic extracts, respectively by GC–MS spectral analysis. Results indicated that the phytoconstituents isolated from the I. sepiaria leaves possess antitubercular activity with no/least toxicity. Overall, three compounds from the PE extract (PE11, PE12, PE14) and two from the EA extract (EA8, EA14) are being proposed as best lead-like phytocompounds based on drug-likeness, synthetic accessibility, and in silico/in vitro correlation. Further optimization studies are needed to develop these phytocompounds as novel antitubercular drugs.