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

Iredia D Iyamu; Yingzhao Zhao; Prakash T Parvatkar; Bracken F Roberts; Debora R Casandra; Lukasz Wojtas; Dennis E Kyle; Debopam Chakrabarti; Roman Manetsch

doi:10.1016/j.bmc.2022.116629

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. Epub 2022 Jan 14.

Authors

Iredia D Iyamu¹, Yingzhao Zhao¹, Prakash T Parvatkar¹, Bracken F Roberts², Debora R Casandra³, Lukasz Wojtas⁴, Dennis E Kyle⁵, Debopam Chakrabarti², Roman Manetsch⁶

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.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Antimalarials / chemical synthesis
Antimalarials / chemistry
Antimalarials / pharmacology*
Cell Survival / drug effects
Chromans / chemical synthesis
Chromans / chemistry
Chromans / pharmacology*
Crystallography, X-Ray
Dose-Response Relationship, Drug
Hep G2 Cells
Humans
Malaria / drug therapy*
Models, Molecular
Molecular Structure
Parasitic Sensitivity Tests
Plasmodium / drug effects*
Spiro Compounds / chemical synthesis
Spiro Compounds / chemistry
Spiro Compounds / pharmacology*
Structure-Activity Relationship

Substances

Antimalarials
Chromans
Spiro Compounds

Abstract

Publication types

MeSH terms

Substances

Grants and funding