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  3. Design, synthesis and evaluation of novel carboline-triazole hybrids as promising antimalarial agents

Design, synthesis and evaluation of novel carboline-triazole hybrids as promising antimalarial agents

  • Eur J Med Chem. 2025 Jun 5:290:117514. doi: 10.1016/j.ejmech.2025.117514.
Ajay Kishor Kushawaha 1,  Rohini Nandi 2,  Arvind Kumar Jaiswal 1,  Hemlata Bhatt 3,  Sarita Katiyar 3,  Alisha Ansari 3,  Abhijit Deb Choudhury 4,  Shabeer Ali 5,  Shikha Mishra 5,  Rabi Sankar Bhatta 6,  Mrigank Srivastava 2,  Satish Mishra 7,  Koneni V Sashidhara 8
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • 2 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002 Uttar Pradesh, India.
  • 3 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002 Uttar Pradesh, India.
  • 4 Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • 5 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • 6 Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002 Uttar Pradesh, India; Pharmaceutics and Pharmacokinetics Division, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India.
  • 7 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002 Uttar Pradesh, India. Electronic address: satish.mishra@cdri.res.in.
  • 8 Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute BS, 10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002 Uttar Pradesh, India; Sophisticated Analytical Instrument Facility & Research, CSIR-Central Drug Research Institute, BS-10/1, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow, 226031,Uttar Pradesh, India. Electronic address: kv_sashidhara@cdri.res.in.
PMID: 40120498 DOI: 10.1016/j.ejmech.2025.117514
Abstract

A series of twenty-four carboline-triazole derivatives were synthesized using a molecular hybridization approach and evaluated for their antimalarial activity against Plasmodium parasites. Ten compounds exhibited strong in vitro antimalarial activity against both chloroquine-sensitive Pf3D7 and chloroquine-resistant PfK1 strains, with IC50 values ranging from 0.21 to 0.98 μM and 0.32-0.82 μM, respectively. Among them, compound 15k demonstrated significant in vivo antimalarial activity against P. yoelii N67 in Swiss mice. Notably, compounds 15e, 15f, and 15k also inhibited P. berghei liver stage development with IC50 values ranging from 4.81 to 7.58 μM. Evaluation of in vitro pharmacokinetic parameters revealed that the synthesized carboline-triazole conjugate 15k fulfils the criteria for orally active drug development. These findings highlight the potential of this scaffold as a promising framework for the development of antimalarial agents.

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