Structure-Activity Relationship of Antischistosomal Ozonide Carboxylic Acids.

Journal of Medicinal Chemistry
Jianbo WuJonathan L Vennerstrom

Abstract

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.

References

Nov 19, 2002·International Journal for Parasitology·Steven R Meshnick
Jun 9, 2006·Bioorganic & Medicinal Chemistry·Yuxiang DongJonathan L Vennerstrom
Feb 7, 2007·Antimicrobial Agents and Chemotherapy·Shu-Hua XiaoMarcel Tanner
Jun 15, 2007·Antimicrobial Agents and Chemotherapy·Marcel KaiserJonathan L Vennerstrom
Feb 13, 2008·Antimicrobial Agents and Chemotherapy·Darren J CreekSusan A Charman
Nov 3, 2009·Nature Reviews. Microbiology·Richard T Eastman, David A Fidock
Mar 23, 2010·Bioorganic & Medicinal Chemistry Letters·Yuxiang DongJonathan L Vennerstrom
Sep 2, 2010·Accounts of Chemical Research·Bernard Meunier, Anne Robert
Feb 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Susan A CharmanJonathan L Vennerstrom
Nov 23, 2011·Antimicrobial Agents and Chemotherapy·Jennifer KeiserJonathan L Vennerstrom
Feb 22, 2012·PLoS Neglected Tropical Diseases·Julien PortelaAnne Robert
Jul 3, 2013·Angewandte Chemie·Sophie A-L Thétiot-LaurentBernard Meunier
Aug 13, 2013·Current Opinion in Microbiology·Nectarios KlonisLeann Tilley
Jun 21, 2014·Parasitology Research·Jian XueShu-hua Xiao
Dec 24, 2015·Nature Communications·Jigang WangQingsong Lin
Feb 24, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Mohamed E M SaeedThomas Efferth
Dec 22, 2016·Angewandte Chemie·Oliver DumeleFrançois Diederich
Jan 5, 2017·Journal of Medicinal Chemistry·Yuxiang DongJonathan L Vennerstrom
Mar 30, 2017·Infectious Diseases of Poverty·Robert BergquistJennifer Keiser
Oct 31, 2017·Parasitology International·A G SanfordP H Davis
Oct 6, 2018·ACS Omega·Jianbo WuJonathan L Vennerstrom
Oct 18, 2019·ACS Infectious Diseases·Carlo GiannangeloDarren J Creek
Oct 19, 2019·ACS Infectious Diseases·Joëlle JourdanPascal Mäser

❮ Previous
Next ❯

Citations

Dec 8, 2020·Angewandte Chemie·Zahid HassanStefan Bräse
Jun 29, 2021·ACS Infectious Diseases·Courtney C Aldrich

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Journal of the Egyptian Society of Parasitology
H M Khalil
Transactions of the Royal Society of Tropical Medicine and Hygiene
H M Gilles
Annals of the New York Academy of Sciences
J Pellegrino, N Katz
© 2021 Meta ULC. All rights reserved