Affiliations 

  • 1 Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia
  • 2 Department of Radiology, Biomedical Research Imaging Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
  • 3 School of Life Sciences, University of Westminster, 115 New Cavendish Street, W1W6 UW London, United Kingdom
  • 4 Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan, Malaysia
  • 5 Department of Parasitology, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 6 Department of Chemical Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia (UKM), Bangi 43600, Selangor, Malaysia. Electronic address: drizz@ukm.edu.my
Bioorg Med Chem Lett, 2024 Dec 01;114:129992.
PMID: 39426430 DOI: 10.1016/j.bmcl.2024.129992

Abstract

Malaria continues to pose a significant threat to global health, which is exacerbated by the emergence of drug-resistant strains, necessitating the urgent development of new therapeutic options. Due to their substantial bioactivity in treating malaria, pyridine and pyrimidine have become the focal point of drug research. Hybrids of pyridine and pyrimidine offer a novel and promising avenue for developing effective antimalarial agents. The ability of these hybrids to overcome drug resistance is tinted, offering a potential solution to this critical obstacle in the treatment of malaria. By targeting multiple pathways, these hybrid compounds reduce the likelihood of resistance development, providing a promising strategy for combating drug-resistant strains of malaria. The review focuses on the most recent developments in 2018 in the structural optimization of pyridine and pyrimidine hybrid compounds, highlighting modifications that have been shown to improve antimalarial activity. Structure-activity studies have elucidated the essential characteristics required for potency, selectivity, and pharmacokinetics. Molecular docking and virtual screening expedite the identification of novel compounds with enhanced activity profiles. This analysis could aid in developing the most effective pyridine and pyrimidine hybrids as antimalarial agents.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.