Schiff Base Ligands As Potential Inhibitors Of Mycobacterium Tuberculosis: DFT, ADMET Profiling, And Molecular Docking Studies

Omobola Ajibike Odedokun, Kayode Taiwo Ishola , Adebomi Ayodeji Ikotun, Chijioke John Ajaelu, Adesoji Adelani Olarenwaju, Titilope Adewumi Ajayi

Abstract


This study deals with the computational design and assessment antibacterial activities of two Schiff base ligands, specifically L1, identified as (E)-3-((4-aminobenzyl)imino)-1-benzylindolin-2-one, and L2, identified as (Z)-3-((4-aminophenyl)imino)-1-benzylindolin-2-one, with the objective of developing potential therapeutic agents against drug-resistant strains of Mycobacterium tuberculosis. Global reactivity parameters, including HOMO/LUMO energies, energy gap, hardness, softness, electronegativity, and electrophilicity of the compounds were ascertained through Density Functional Theory (DFT) computations executed with the ORCA 6.1.1 software package. The SwissADME and ProTox 3.0 platforms were utilized for ADMET profiling to evaluate physicochemical, pharmacokinetic, and toxicological characteristics of the compounds. Molecular docking simulations were conducted against the M. tuberculosis target protein in Dockey. Both ligands were found to adhere to Lipinski's rule of five, suggesting favorable oral bioavailability, and exhibited binding affinities of −9.04 kcal/mol for L1 and −8.82 kcal/mol for L2, thereby exceeding that of the established drug isoniazid (−6.57 kcal/mol). These results indicate that while L1 and L2 serve as promising foundational structures for the development of anti-TB therapeutics, subsequent structural refinement and measures to mitigate toxicity are imperative prior to progression to preclinical stages.

Keywords


ADMET, Docking, Ligand, Tuberculosis, Toxicity

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References


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DOI: http://dx.doi.org/10.52155/ijpsat.v57.2.8228

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