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Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)

Copyright (c) 2026 Vijaya Jyothi Mallela, Triveni, Vijaya Bhaskar Kuruba, Azger Dusthackeer Vijayan Nynar, Naresh Babu Chilamakuru

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This work is licensed under a Creative Commons Attribution 4.0 International License.

Synthesis of Triazolylazetidinones as Promising Antitubercular Agents: Computational and Experimental Validation Targeting Polyphosphate Kinase 2

https://doi.org/10.14233/ajchem.2026.36406
Triveni Singirisetty
Manipal Academy of Higher Education, Manipal-576104, India; RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research Campus, Ananthapuramu-515721, India
https://orcid.org/0000-0002-2805-4217
Vijaya Bhaskar Kuruba
Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal-576104, India
https://orcid.org/0000-0002-3982-0845
Azger Dusthackeer Vijayan Nynar
ICMR-National Institute for Research in Tuberculosis (NIRT), Chennai-600031, India
https://orcid.org/0000-0002-3616-3675
Naresh Babu Chilamakuru
Department of Pharmaceutical Chemistry, RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research campus, Ananthapuramu-515721, India
https://orcid.org/0000-0002-8496-053X
Vijaya Jyothi Mallela
Department of Pharmaceutical Chemistry, RERDS-CPR, Raghavendra Institute of Pharmaceutical Education and Research campus, Ananthapuramu-515721, India
https://orcid.org/0000-0002-9693-2333

Corresponding Author(s) : Vijaya Jyothi Mallela

drmvjyothiriper@gmail.com

Asian Journal of Chemistry, Vol. 38 No. 8 (2026): Vol 38, Issue 8 (2026)

Abstract

A series of novel 1,2,4-triazole-azetidin-2-one hybrids (A1-A12) were designed and synthesised as potential anti-tubercular agents. The compounds were synthesised via Schiff base formation followed by cyclocondensation reactions. The compounds were studied as anti-tubercular agents against polyphosphate kinase 2 (PPK2), an enzyme involved in nucleotide regulation in Mycobacterium tuberculosis. A three-dimensional model of PPK2 was generated and examined by molecular dynamics studies. Docking studies indicated favourable interactions of some compounds with amino acid residues ASN131, GLU136, LYS75 and ARG127 in the active site of PPK2, supporting their possible role as PPK2 inhibitors. ADMET simulation analysis revealed favourable physico-chemical and pharmacokinetic parameters, satisfying the criteria for oral drug-likeness. The anti-tubercular activity of compounds A1-A12 was evaluated against M. tuberculosis H37Rv using the minimum inhibitory concentration (MIC) method. Compounds A11 and A12 exhibited the highest activity with MIC values below 7.81 μg/mL, while the remaining derivatives showed moderate to weak activity. Cytotoxicity studies on Vero cells demonstrated concentration-dependent effects, and IC50 values indicated acceptable selectivity for compounds A1 and A12. Acute oral toxicity studies in mice established an LD50 value of 300 mg/kg. Histopathological examination of major organs revealed no significant structural changes at tolerated doses.

Keywords

Triazole Azetidinones Polyphosphate kinase 2 Molecular docking ADMET profiling Antitubercular activity
(1)
Singirisetty, T.; Kuruba, V. B.; Vijayan Nynar, A. D.; Chilamakuru, N. B.; Mallela, V. J. Synthesis of Triazolylazetidinones As Promising Antitubercular Agents: Computational and Experimental Validation Targeting Polyphosphate Kinase 2. ajc 2026, 38, 2131-2145.
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