In Silico Approach: Anti-Tuberculosis Activity of Caespitate in the H37Rv Strain

Area of Science:

• Pharmacology
• Natural Products Chemistry
• Microbiology

Background:

• Tuberculosis (TB) remains a significant global health threat, caused by Mycobacterium tuberculosis (Mtb).
• Caespitate, a phytochemical from Helichrysum caespititium, exhibits anti-tubercular activity, but its mechanism of action is unclear.
• Potential Mtb targets include enzymes involved in cell wall synthesis (InhA, MabA, UGM) and cell growth (PanK).

Purpose of the Study:

• To investigate the molecular interactions of caespitate with potential Mtb targets.
• To determine the preferred conformation of caespitate for drug interaction.
• To evaluate the pharmacokinetic properties and potential of caespitate as an anti-TB agent.

Main Methods:

• Density Functional Theory (DFT) for conformational analysis of caespitate.
• Molecular docking to predict binding interactions with Mtb enzymes.
• Molecular Mechanics with Generalized Born Surface Area (MM/GBSA) for stability assessment.
• ADME (Absorption, Distribution, Metabolism, Excretion) parameter evaluation.

Main Results:

• The solution conformation (CS) of caespitate was favored for interactions with PanK and UGM.
• Stable complexes were formed between caespitate and both PanK and UGM, maintaining key intramolecular hydrogen bonds.
• Caespitate demonstrated favorable pharmacokinetic properties, indicating good absorption, permeability, and bioavailability.
• Potential antibacterial and antimonial activities were also suggested.

Conclusions:

• Caespitate shows promise as a lead compound for developing novel anti-tuberculosis drugs.
• PanK and UGM are identified as key molecular targets for caespitate's anti-tubercular activity.
• This research supports the exploration of natural products for new anti-TB drug discovery.