Chroman-Schiff base derivatives as potential Anti-Tubercular Agents: In silico studies, Synthesis, and Biological...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Microbiology

Background:

• Tuberculosis (TB) remains a global health crisis, necessitating novel therapeutic strategies.
• Hydrazide-containing compounds have shown potential against TB.
• Chroman-Schiff base derivatives offer a novel scaffold for anti-TB drug development.

Purpose of the Study:

• To design, synthesize, and evaluate novel chroman-Schiff base derivatives as potential anti-TB agents.
• To investigate the binding interactions of these derivatives with the TB target protein InhA using in silico methods.
• To assess the in vitro anti-tubercular activity of the synthesized compounds.

Main Methods:

• Synthesis and structural validation of chroman-Schiff base derivatives using spectroscopic techniques (FTIR, NMR, HR-MS).
• In silico studies including molecular docking and molecular dynamics simulations against the InhA protein (PDB ID: 1ZID).
• In vitro anti-tubercular assays against Mycobacterium tuberculosis H37Rv using the Microplate Alamar Blue Assay (MABA).

Main Results:

• Molecular docking identified R-isomer derivatives (SM-5A, SM-6A) with superior binding affinities to InhA compared to reference ligands.
• Molecular dynamics simulations confirmed the stability of these compound-protein complexes over 100 ns.
• In vitro assays revealed potent anti-TB activity for SM-2 and SM-5, with minimum inhibitory concentrations (MIC) of 32 µg/mL, comparable to standard drugs.

Conclusions:

• The chroman-Schiff base scaffold is a promising foundation for developing new anti-TB therapeutics.
• Computational and experimental data support the potential of these derivatives for further optimization.
• The synthesized compounds demonstrate significant potential as novel anti-tubercular agents.