Discovery of new diaminoquinazolines against Mycobacterium tuberculosis: chemical synthesis and in vitro evaluation.

Authors

Mukul Kore, Niranjana Sri Sundaramoorthy, Saqib Kidwai, Ramandeep Singh, Sandeep Sundriyal

Published in

RSC advances. Volume 16. Issue 43. Pages 53687-53710. Sep 30, 2026. Epub Sep 09, 2026.

Abstract

Despite the availability of multiple treatment options, the emergence of drug-resistant Mycobacterium tuberculosis (Mtb) strains presents a significant health concern worldwide. This necessitates the development of novel antitubercular agents with distinct mechanisms of action. Diaminoquinazolines (DAQs) have demonstrated antimicrobial and antiparasitic potential, yet their exploration against Mtb remains underexplored. To expand the DAQ SAR, we have synthesized diverse derivatives featuring novel C2/C4 amine combinations and core modifications and evaluated their activity against Mtb. SAR analysis identified 1-benzylpiperidin-4-amine at C4 paired with 4-phenoxyaniline at C2 as optimal, delivering analogues 14c and 14f-14k with potent activity against wild-type and MDR Mtb strains. The analogues were also active against M. bovis BCG harboring mutations in mmpL3, hadC and katG, indicating these targets are not involved in DAQs mechanism of action. Therefore, these DAQ analogues offer promising starting points for the design of molecules against drug-resistant tuberculosis.

PMID:
42719720
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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