International Journal of Drug Delivery Technology
Volume 16, Issue 10s, 2026

Design, Synthesis, and Biological Evaluation of Luminescent Chalcone-Based Novel Pyridine Derivatives Targeting DprE1 Enzyme Against H37Rv Strain of Mycobacterium Tuberculosis

Chilamakuri Nareshbabu1, Chelluru Anusree1, Kariyannagari Dhanunjay1, Mallela Vijaya Jyothi2*

1Department of Pharmaceutical Chemistry, Raghavendra Institute of Pharmaceutical Education and Research, Anantapuramu, Andhra Pradesh, India - 515721

2*Raghavendra Institute of Pharmaceutical Education and Research – Autonomous, K.R. Palli Cross, Chiyyedu, Anantapuramu, A.P. - 515721. Email: drmvjyothiriper@gmail.com (Corresponding Author)

ABSTRACT

Chalcones are versatile scaffolds in medicinal chemistry, owing to their reactive α,β-unsaturated carbonyl group and potential to form diverse nitrogen-containing heterocycles with significant pharmacological properties. In this study, thirty novel derivatives including indazolopyridines, cyanopyridines, and triazolopyridines—were synthesized from ten 2-acetylpyridine-based chalcones and evaluated for their anti-tubercular potential. The transformation of chalcones into these heterocycles involved nucleophilic cyclization followed by aromatization, exploiting the electrophilic β-carbon of the enone system. Molecular docking studies demonstrated favorable interactions with DprE1, a critical enzyme in Mycobacterium tuberculosis cell wall biosynthesis, indicating potential inhibitory efficacy. In silico ADME analysis confirmed drug-like properties, including high gastrointestinal absorption, solubility, and Lipinski compliance. Structural characterization was achieved through IR, ¹H NMR, ¹³C NMR, and mass spectrometry. Luciferase reporter assay revealed potent antitubercular activity of several pyridine derivatives, notably I7, I8, P1, and C8, exhibiting over 95% inhibition against M. tuberculosis H37Rv. SAR analysis indicated that conjugated, donor–acceptor-rich scaffolds with strong luminescence also enhanced target affinity, suggesting promising theranostic potential.

Keywords: Chalcones, Anti-tubercular agent, Mycobacterium tuberculosis, DprE1, Molecular Docking

How to cite this article: Nareshbabu C, Anusree C, Dhanunjay K, Jyothi MV. Design, Synthesis, and Biological Evaluation of Luminescent Chalcone-Based Novel Pyridine Derivatives Targeting DprE1 Enzyme Against H37Rv Strain of Mycobacterium Tuberculosis. Int J Drug Deliv Technol. 2026;16(10s): 692. DOI: 10.25258/ijddt.16.10s.83

Source of support: Nil.

Conflict of interest: Nil