Structure-activity and structure-property relationship studies of spirocyclic chromanes with antimalarial activity

  • Bioorg Med Chem. 2022 Mar 1;57:116629. doi: 10.1016/j.bmc.2022.116629.
Iredia D Iyamu  1 ,  Yingzhao Zhao  1 ,  Prakash T Parvatkar  1 ,  Bracken F Roberts  2 ,  Debora R Casandra  3 ,  Lukasz Wojtas  4 ,  Dennis E Kyle  5 ,  Debopam Chakrabarti  2 ,  Roman Manetsch  6
Affiliations
  • 1. Department of Chemistry and Chemical Biology, College of Science, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
  • 2. Molecular Microbiology Division, Burnett School of Biomedical Science, University of Central Florida, 12722 Research Parkway, Orlando, FL 32826, USA.
  • 3. Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Tampa, FL 33612, USA.
  • 4. Department of Chemistry, University of South Florida, 4202 E. Fowler Ave, Tampa, FL 33620, USA.
  • 5. Department of Global Health, College of Public Health, University of South Florida, 3720 Spectrum Boulevard, Tampa, FL 33612, USA; Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, 500 D.W. Brooks Dr, Athens, GA 30602, USA.
  • 6. Department of Chemistry and Chemical Biology, College of Science, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Department of Pharmaceutical Sciences, Bouvé College of Pharmacy, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA; Center for Drug Discovery, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, USA.
PMID: 35091169 DOI: 10.1016/j.bmc.2022.116629
Abstract

Malaria is a prevalent and lethal disease. The fast emergence and spread of resistance to current therapies is a major concern and the development of a novel line of therapy that could overcome, the problem of drug resistance, is imperative. Screening of a set of compounds with drug/natural product-based sub-structural motifs led to the identification of spirocyclic chroman-4-one 1 with promising antimalarial activity against the chloroquine-resistant Dd2 and chloroquine-sensitive 3D7 strains of the Parasite. Extensive structure-activity and structure-property relationship studies were conducted to identify the essential features necessary for its activity and properties.

Keywords
Antimalarial; Drug resistance; Natural products; Spirocyclic chromane; Structure-activity relationship; Structure-property relationship.
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