Synthesis and Anti-Mycobacterium Activity of Some New N-Rich Heterocyclic Derivatives and Their Molecular Docking, and DFT Studies

Objective: Synthesis of N-rich heterocyclic derivatives; anti-TB activity, molecular docking, ADME-T, and computational studies. Methods: Synthesis was carried out by conventional method; structures of synthesised was confirmed by different spectroscopic methods; evaluation of anti-TB activity was done by Microplate Alamar Blue assay (MABA); Molecular docking was analyzed by using ChemBioDraw tool (part of the ChemBioOffice Ultra 14.0 suite) and ADME was done by web programme Swiss ADME; DFT studies was carried out by DFT (B3LYP) with the aid of the 6-311++G(d,p) basis set in the Gaussian 09 software. Results: The activity results showed that compounds (IIIc) and (IIIe) demonstrated outstanding activity with MIC values of 1.6 μg/mL, which are closer to the reference standards of rifampicin and streptomycin, while the remaining compounds had reduced efficacy. Discussion: These results show that activity affected by the pyrimidine core and indole moiety of (IIIc) and (IIIe) showed very effective efficacy compared to the reference standards, respectively. Conclusions: Based on the anti-TB activity findings, in-silico molecular docking and ADME profiles, our synthesized drugs followed all five criteria, including high GI absorption, no blood-brain barrier, and minimal skin permeability. Compounds (IIIa) and (IIIb) demonstrated a smaller energy gap in the DFT analysis, indicating that it is chemically more reactive than other compounds. As a result, these compounds demonstrated increased anti-TB activity.