2. Academic Validation
  3. Synthesis, biological evaluation, Structure - Activity relationship studies of quinoline-imidazole derivatives as potent antimalarial agents

Synthesis, biological evaluation, Structure - Activity relationship studies of quinoline-imidazole derivatives as potent antimalarial agents

  • Bioorg Chem. 2022 Apr;121:105671. doi: 10.1016/j.bioorg.2022.105671.
Deblina Roy 1,  Mohammad Anas 2,  Ashan Manhas 2,  Satyen Saha 3,  Niti Kumar 4,  Gautam Panda 5
Affiliations

Affiliations

  • 1 Medicinal and Process Chemistry Division and CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India; Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, UP, India.
  • 2 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India.
  • 3 Department of Chemistry, Institute of Science, Banaras Hindu University, Varanasi 221005, UP, India.
  • 4 Division of Molecular Microbiology and Immunology, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India. Electronic address: [email protected].
  • 5 Medicinal and Process Chemistry Division and CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Sitapur Road, Lucknow 226031, India; Academy of Scientific and Innovative Research, New Delhi 110001, India. Electronic address: [email protected].
PMID: 35168120 DOI: 10.1016/j.bioorg.2022.105671
Abstract

In our efforts to identify novel chemical scaffolds for the development of antimalarial agents, a series of quinoline - imidazole hybrid compounds were synthesized and their blood-stage antimalarial activity was evaluated in both drug-sensitive and -multi drug-resistant (MDR) P. falciparum strains. The new analogs possess sub-micromolar activities against Plasmodium falciparum. Among all synthesized derivatives, 11(xxxii) exhibited significant antimalarial efficacy in-vitro against both CQ-sensitive (IC50-0.14 μM) and MDR strain (IC50- 0.41 μM) with minimal cytotoxicity and high selectivity. Structure-activity relationships revealed that Br and OMe substitutions on quinoline ring improved the antimalarial activity and selectivity index. The role of stereochemistry in the inhibitory activity was assessed by enantiomeric separation of a racemic mixture of 11(xxxii). The enantiomer (-)-11(xxxii) had potent antimalarial activity over the other isomer, with IC50 of 0.10 µM.

Keywords

Antimalarial agents; Quinoline-imidazole hybrids; Structure−Activity relationship.

Figures
Products