In silico Anti-tubercular studies for Selected Phytoconstituents from Diospyros paniculata and assessment of In vitro activity for the extract

Abstract

Background: Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains one of the leading causes of death from infectious diseases globally. Increasing resistance to conventional anti-TB drugs highlights the urgent need for novel therapeutic agents. Diospyros paniculata, a medicinal plant known for its diverse phytochemical profile, was selected for investigation due to its traditional therapeutic relevance and reported presence of naphthoquinones and triterpenes. Materials and Methods: A comprehensive literature review identified bioactive phytoconstituents of D. paniculata, which were then evaluated for pharmacokinetic properties using the QikProp module (Schrodinger). Selected compounds were subjected to molecular docking studies using Maestro 12.4 against TB-associated protein targets (PDB ID: 4B6C). Network pharmacology was applied to determine relevant gene and pathway interactions. Methanolic extracts of the plant’s bark and leaves were prepared and tested in vitro for anti-tubercular activity using the Microplate Alamar Blue Assay (MABA) against the M. tuberculosis H37Rv strain. Results: Docking results revealed strong binding interactions of compounds such as Diospyrin and 5-hydroxy-4-methoxy-2-naphthaldehyde with key amino acid residues. ADME profiling suggested favorable permeability of triterpenes, though limited solubility may affect oral bioavailability. The MABA assay demonstrated that the leaf extract had a minimum inhibitory concentration (MIC) of 25 µg/mL, while the bark extract showed an MIC of 50 µg/mL. The standard drug, Isoniazid, exhibited an MIC of 1.6 µg/mL. Conclusion: The study highlights the promising anti-tubercular potential of Diospyros paniculata, especially its leaf extract. These findings warrant further investigation for compound isolation, mechanistic studies, and in-vivo validation to support drug development efforts.