Distribution and quantitation of the anti-trypanosomal diamidine 2,5-bis(4-amidinophenyl)furan (DB75) and its N-methoxy prodrug DB289 in murine brain tissue

Acta Tropica
Lisa M SturkRichard R Tidwell

Abstract

The current epidemic of sleeping sickness, also known as human African trypanosomiasis in sub-Saharan Africa places nearly 60 million people at risk for developing this life threatening infection. Although effective treatments for early-stage sleeping sickness exist, these drugs usually require extended dosing schedules and intravenous administration. New treatments are also needed for cerebral (late) stage trypanosomiasis. 2,5-Bis(4-amidinophenyl)furan (DB75), a pentamidine analog, has potent in vitro and in vivo anti-trypanosomal activity. However, DB75 does not exhibit significant oral bioavailability and has proved to be ineffective against mouse models of late-stage sleeping sickness regardless of administration route. To circumvent the limited oral bioavailability of DB75, an N-methoxy prodrug 2,5-bis(4-amidinophenyl)furan-bis-O-methylamidoxime (DB289) was designed and developed initially as a compound to treat AIDS-related Pneumocystis carinii pneumonia (PCP). Despite excellent oral activity against early-stage sleeping sickness, oral administration of DB289 exhibited limited efficacy in mouse models of late-stage disease. DB289 has recently entered Phase II(b) clinical trials to treat primary-stage sleeping sickness in ...Continue Reading

References

Apr 1, 1977·Journal of Medicinal Chemistry·B P Das, D W Boykin
Jan 1, 1990·Annals of the New York Academy of Sciences·R R TidwellJ E Hall
Sep 1, 1985·Reviews of Infectious Diseases·M SandsR B Brown
Feb 14, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lizette GranbergEva B Brittebo

❮ Previous
Next ❯

Citations

Nov 3, 2006·Nature Reviews. Drug Discovery·Solomon Nwaka, Alan Hudson
Jun 2, 2010·The Journal of Antimicrobial Chemotherapy·Hiroshi NishikawaJunichi Mitsuyama
May 26, 2006·Antimicrobial Agents and Chemotherapy·Amanda M MathisJames Edwin Hall
Apr 7, 2010·Antimicrobial Agents and Chemotherapy·Michael Zhuo WangKarl A Werbovetz
Aug 19, 2007·Antimicrobial Agents and Chemotherapy·Alexandra LüscherPascal Mäser
Oct 24, 2007·Antimicrobial Agents and Chemotherapy·Janice R SufrinCyrus J Bacchi
Jan 30, 2008·Antimicrobial Agents and Chemotherapy·Junichi MitsuyamaHirokazu Narita
Jul 30, 2005·Expert Opinion on Investigational Drugs·M N C SoeiroD W Boykin
Jul 10, 2007·British Journal of Pharmacology·M P BarrettR R Tidwell
Dec 1, 2006·Advances in Parasitology·Michael P Barrett, Ian H Gilbert
Jan 11, 2005·Current Opinion in Infectious Diseases·J Jannin, P Cattand
Nov 17, 2006·Nature Chemical Biology·Adam R Renslo, James H McKerrow
Aug 17, 2006·Molecular Pharmacology·Charlotte A LanteriMichael P Barrett
Jan 23, 2020·Tropical Medicine and Infectious Disease·Harry P De Koning
Dec 23, 2019·RSC Medicinal Chemistry·Mousmee Sharma, Parteek Prasher
Jul 22, 2005·Journal of Medicinal Chemistry·Svea MeieringR Luise Krauth-Siegel

❮ Previous
Next ❯

Related Concepts

Related Feeds

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Related Papers

Xenobiotica; the Fate of Foreign Compounds in Biological Systems
John H AnsedeJames Edwin Hall
Tropical Medicine & International Health : TM & IH
Reto BrunC Burri
Tropical Medicine & International Health : TM & IH
A Stanghellini, T Josenando
Expert Opinion on Investigational Drugs
M N C SoeiroDavid W Boykin
© 2022 Meta ULC. All rights reserved