Papireddy, Kancharla, Smilkstein, Martin, Kelly, Jane XU, Shweta, Dr., Salem, Shaimaa M., Alhamadsheh, Mamoun, Haynes, Stuart W., Challis, Gregory L. and Reynolds, Kevin A.. (2011) Antimalarial activity of natural and synthetic prodiginines. Journal of Medicinal Chemistry, Vol.54 (No.15). pp. 5296-5306. ISSN 0022-2623

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Abstract

Prodiginines are a family of linear and cyclic oligopyrrole red-pigmented compounds. Herein we describe the in vitro antimalarial activity of four natural (IC(50) = 1.7-8.0 nM) and three sets of synthetic prodiginines against Plasmodium falciparum. Set 1 compounds replaced the terminal nonalkylated pyrrole ring of natural prodiginines and had diminished activity (IC(50) > 2920 nM). Set 2 and set 3 prodiginines were monosubstituted or disubstituted at either the 3 or 5 position of the right-hand terminal pyrrole, respectively. Potent in vitro activity (IC(50) = 09-16.0 nM) was observed using alkyl or aryl substituents. Metacycloprodiginine and more potent synthetic analogues were evaluated in a P. yoelii murine patent infection using oral administration. Each analogue reduced parasitemia by more than 90% after 2S (mg/kg)/day dosing and in some cases provided a cure. The most favorable profile was 92% parasite reduction at 5 (mg/kg)/day, and 100% reduction at 2S (mg/kg)/day without any evident weight loses or clinical overt toxicity.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry R Medicine > RC Internal medicine R Medicine > RM Therapeutics. Pharmacology
Divisions:	Faculty of Science > Chemistry
Library of Congress Subject Headings (LCSH):	Antimalarials, Malaria, Plasmodium falciparum, Streptomyces, Apoptosis, Antibiotics -- Synthesis
Journal or Publication Title:	Journal of Medicinal Chemistry
Publisher:	American Chemical Society
ISSN:	0022-2623
Date:	11 August 2011
Volume:	Vol.54
Number:	No.15
Page Range:	pp. 5296-5306
Identification Number:	10.1021/jm200543y
Status:	Peer Reviewed
Publication Status:	Published
Funder:	National Institutes of Health (U.S.) (NIH)
Grant number:	GM077147 (NIH)
URI:	http://wrap.warwick.ac.uk/id/eprint/38532

Data sourced from Thomson Reuters' Web of Knowledge

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