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

• DOI: 10.1016/j.bmc.2022.116629
• Publication Date: 2022-01-14T07:26:44Z
• Authors: Iredia D. Iyamu; Yingzhao Zhao; Prakash T. Parvatkar; Bracken F. Roberts; Debora R. Casandra; Lukasz Wojtas; Dennis E. Kyle; Debopam Chakrabarti; Roman Manetsch
• Keywords: Models, Molecular; 0301 basic medicine; Plasmodium; Dose-Response Relationship, Drug; Molecular Structure; Cell Survival; Hep G2 Cells; Crystallography, X-Ray; Malaria; 3. Good health; Antimalarials; Structure-Activity Relationship; 03 medical and health sciences; Parasitic Sensitivity Tests; Humans; Spiro Compounds; Chromans

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.