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

• Published in: Bioorganic & medicinal chemistry Vol. 57; p. 116629
• Main Authors: Iyamu, Iredia D., Zhao, Yingzhao, Parvatkar, Prakash T., Roberts, Bracken F., Casandra, Debora R., Wojtas, Lukasz, Kyle, Dennis E., Chakrabarti, Debopam, Manetsch, Roman
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.03.2022; Elsevier
• Subjects: Antimalarial; Antimalarials - chemical synthesis; Antimalarials - chemistry; Antimalarials - pharmacology; Biochemistry & Molecular Biology; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Chromans - chemical synthesis; Chromans - chemistry; Chromans - pharmacology; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug resistance; Hep G2 Cells; Humans; Life Sciences & Biomedicine; Malaria - drug therapy; Models, Molecular; Molecular Structure; Natural products; Parasitic Sensitivity Tests; Pharmacology & Pharmacy; Physical Sciences; Plasmodium - drug effects; Science & Technology; Spiro Compounds - chemical synthesis; Spiro Compounds - chemistry; Spiro Compounds - pharmacology; Spirocyclic chromane; Structure-Activity Relationship; Structure-property relationship; Antimalarial; Structure-property relationship; Drug resistance; Natural products; Spirocyclic chromane; Structure-activity relationship; ENANTIOSELECTIVE SYNTHESIS; NATURAL-PRODUCTS; OPTIMIZATION
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2022.116629

[Display omitted] 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.