Abstract
An in vivo-in vitro model was used to assess the antimalarial activity of PS-15 and its metabolite, WR99210, against Plasmodium falciparum. WR99210, an antifolate triazine compound, was given as a single oral dose of 30 mg/kg to 8 Saimiri sciureus monkeys and, 3 months later, the parent compound, PS-15, was given similarly to the same monkeys. Serum samples were collected at various times after drug administration, serially diluted with control serum, and their antimalarial activity in vitro was determined against the multidrug-resistant K1 isolate of P. falciparum. Serum concentrations of PS-15 and WR99210 were estimated by high performance liquid chromatography. The maximum dilutions of serum that inhibited parasite growth were 20- to 86-fold higher 3 and 6 h after administration of PS-15 than following WR99210 administration. Substantial serum antimalarial activity was observed even at 48 h after medication with PS-15. Serum drug concentrations provided further evidence that PS-15 was absorbed far better from the gastrointestinal tract than WR99210. The substantial and sustained activity of PS-15 suggests that a single dose, or several smaller doses given once a day, should be effective in curing drug-resistant infections of...Continue Reading
References
Jan 7, 1978·Lancet·K H RieckmannJ E Mrema
Aug 20, 1976·Science·W Trager, J B Jensen
Apr 1, 1986·Annals of Tropical Medicine and Parasitology·G E Childs, C Lambros
May 15, 1987·Journal of Chromatography·R B TaylorN A Ochekpe
Jan 1, 1981·Transactions of the Royal Society of Tropical Medicine and Hygiene·S Thaithong, G H Beale
Mar 1, 1995·Chemotherapy·B M Kotecka, K H Rieckmann
Feb 1, 1994·The American Journal of Tropical Medicine and Hygiene·M D EdsteinK H Rieckmann
Jul 1, 1993·The American Journal of Tropical Medicine and Hygiene·C J CanfieldD P Jacobus
Citations
Mar 20, 2001·Molecular and Biochemical Parasitology·J T FerlanC H Sibley
Sep 12, 2001·Molecular and Biochemical Parasitology·E G HankinsC H Sibley
Sep 25, 1998·Molecular and Biochemical Parasitology·J F Cortese, C V Plowe
Feb 19, 2005·Drug Discovery Today·Amy C Anderson
Oct 5, 2012·Proceedings of the National Academy of Sciences of the United States of America·Yongyuth YuthavongDavid Matthews
Aug 17, 2002·Antimicrobial Agents and Chemotherapy·Liang MaJoseph A Kovacs
Aug 11, 2012·PLoS Neglected Tropical Diseases·Douglas H KerlinMichelle L Gatton
Apr 11, 2014·Chemical Biology & Drug Design·Wanwimon MokmakSumalee Kamchonwongpaisan
Feb 1, 2008·Expert Opinion on Therapeutic Patents·David B BolstadAmy C Anderson
Oct 22, 2014·Journal of Biomolecular Structure & Dynamics·Sheenu AbbatPrasad V Bharatam
Oct 19, 2002·Memórias do Instituto Oswaldo Cruz·S D Srinivas, S K Puri
May 9, 2008·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Man Chin ChungLorena Blau
May 19, 2018·FEBS Letters·Akira SogaShinya Fukumoto
May 31, 2018·Angewandte Chemie·Stefano AgnelloRainer Riedl
Nov 17, 2007·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Damaris S DiazTodd W Shearer
Sep 2, 2020·Biochemical Society Transactions·Petar P S CalicSheena McGowan
Sep 24, 2015·Acta Crystallographica. Section E, Crystallographic Communications·Pattarapol KhongsukPalangpon Kongsaeree
Oct 21, 2020·Antimicrobial Agents and Chemotherapy·T Parks RemchoKristin D Lane
Oct 23, 1997·Antimicrobial Agents and Chemotherapy·M D EdsteinK H Rieckmann
Aug 8, 2021·European Journal of Medicinal Chemistry·Oleksandr GrytsaiRachid Benhida
Nov 2, 2001·Journal of Medicinal Chemistry·N P JensenD P Jacobus