Background: Benzothiazole derivatives are known for anti-TB properties. Based on the
known anti-TB benzothiazole pharmacophore, in the present study, we described the synthesis,
structural elucidation, and anti-tubercular screening of a series of novel benzothiazole (BNTZ) derivatives
(BNTZ 1–7 and BNTZ 8–13).
Objective: The study aims to carry out the development of benzothiazole based anti-TB compounds.
Methods: Title compounds are synthesized by microwave method and purified by column chromatography.
Characterization of the compounds is achieved by FT-IR, NMR (1H and 13C), LCMS
and elemental analysis. Screening of test compounds for anti-TB activity is achieved by Resazurin
Microplate Assay (REMA) Plate method.
Results: It was noted that the BNTZ compound with an isoquinoline nucleus (BNTZ 9) exhibited
remarkable anti-tubercular activity at 8 μg/mL against both the susceptible strain H37Rv and the
multi-drug resistant tuberculosis strains of Mycobacterium tuberculosis. On the other hand, the
BNTZ compound with a naphthalene nucleus (BNTZ 2) revealed anti-tubercular activity at 6
μg/mL and 11 μg/mL against both the susceptible strain H37Rv and the multi-drug resistant tuberculosis
strains of M. tuberculosis, respectively. One of the selected BNTZ derivatives BNTZ 13
was used for single crystal X-ray studies.
Conclusion: To identify the appropriate target for potent BNTZ compounds from the series, molecular
modeling studies revealed the multiple strong binding of several BNTZs with mycobacterium
lysine-ɛ-aminotransferase and decaprenyl-phosphoryl-β-D-ribose 2'-oxidase. The interaction
is derived by forming favorable hydrogen bonds and stacking interactions. This new class of
BNTZ compounds gave promising anti-tubercular actions in the low micromolar range, and can be
further optimized on a structural basis to develop promising, novel, BNTZ pharmacophore-based