The Multi-Drug resistance ability of Mycobacterium tuberculosis (Mtb) has made it a world challenge. DHFR inhibitors received attention as Methotrexate (MTX) was found to inhibit the activity of Dihydrofolate Reductase (DHFR). This research uses Quantitative Structure-Activity Relationship (QSAR), Molecular docking, and Pharmacokinetics to design some compounds as DHFR inhibitors. Four molecular descriptors were used to build a QSAR model. The QSAR results show that all the parameters required of a QSAR model were met. The model was used to design three (3) compounds using the Ligand-Based Drug Design (LBDD) approach. The compounds were evaluated with Molecular docking, Pharmacokinetics, and results were compared with the template compound (9) and reference drugs (Isoniazid-INH, Trimethoprim-TMP, and Methotrexate-MTX). It was found that the designed compounds gave better bioactivity and binding affinity than the template compound and reference drugs. Pharmacokinetics evaluation of the compounds confirmed that they are orally active using Lipinski’s rule of five.<br/>As a result of these computational approaches, new DHFR inhibitors with improved bioactivity can be synthesized as anti-tuberculosis candidates.

Design of novel DHFR inhibitors as anti-tuberculosis: QSAR, molecular docking, and pharmacokinetic studies

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