Biomaterial Database

Structure-Activity Relationship of Antischistosomal Ozonide Carboxylic Acids. 2020

Jianbo Wu, and Xiaofang Wang, and Francis C K Chiu, and Cécile Häberli, and David M Shackleford, and Eileen Ryan, and Sriraghavan Kamaraj, and Vivek J Bulbule, and Alexander I Wallick, and Yuxiang Dong, and Karen L White, and Paul H Davis, and Susan A Charman, and Jennifer Keiser, and Jonathan L Vennerstrom

College of Pharmacy, University of Nebraska Medical Center, Nebraska Medical Center, Omaha, Nebraska 986125, United States.

Semisynthetic artemisinins and other bioactive peroxides are best known for their powerful antimalarial activities, and they also show substantial activity against schistosomes-another hemoglobin-degrading pathogen. Building on this discovery, we now describe the initial structure-activity relationship (SAR) of antischistosomal ozonide carboxylic acids OZ418 (2) and OZ165 (3). Irrespective of lipophilicity, these ozonide weak acids have relatively low aqueous solubilities and high protein binding values. Ozonides with para-substituted carboxymethoxy and N-benzylglycine substituents had high antischistosomal efficacies. It was possible to increase solubility, decrease protein binding, and maintain the high antischistosomal activity in mice infected with juvenile and adult Schistosoma mansoni by incorporating a weak base functional group in these compounds. In some cases, adding polar functional groups and heteroatoms to the spiroadamantane substructure increased the solubility and metabolic stability, but in all cases decreased the antischistosomal activity.

UI	MeSH Term	Description	Entries
D002264	Carboxylic Acids	Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic.	Carboxylic Acid,Acid, Carboxylic,Acids, Carboxylic
D005260	Female		Females
D006573	Heterocyclic Compounds, 1-Ring	Organic compounds that contain a ring structure made up of carbon and one or more additional elements such as nitrogen and oxygen.	Heterocyclic Cpds, 1-Ring,1-Ring Heterocyclic Compounds,1-Ring Heterocyclic Cpds,Heterocyclic Compounds, 1 Ring,Heterocyclic Cpds, 1 Ring
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000218	Adamantane	A tricyclo bridged hydrocarbon.	Diamantane
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012550	Schistosoma mansoni	A species of trematode blood flukes of the family Schistosomatidae. It is common in the Nile delta. The intermediate host is the planorbid snail. This parasite causes schistosomiasis mansoni and intestinal bilharziasis.	Schistosoma mansonus,mansonus, Schistosoma
D012555	Schistosomiasis mansoni	Schistosomiasis caused by Schistosoma mansoni. It is endemic in Africa, the Middle East, South America, and the Caribbean and affects mainly the bowel, spleen, and liver.	Schistosomiasis, Intestinal,Schistosoma mansoni Infection,Infection, Schistosoma mansoni,Infections, Schistosoma mansoni,Intestinal Schistosomiases,Intestinal Schistosomiasis,Schistosoma mansoni Infections,Schistosomiases, Intestinal
D012556	Schistosomicides	Agents that act systemically to kill adult schistosomes.	Antischistosomal Agent,Antischistosomal Agents,Schistosomicide,Agent, Antischistosomal,Agents, Antischistosomal
D013141	Spiro Compounds	Cyclic compounds that include two rings which share a single atom (usually a carbon). The simplest example of this type of compound is Spiro[2.2]pentane, which looks like a bow tie.	Compounds, Spiro