Dicationic biphenyl benzimidazole derivatives as antiprotozoal agents

Bioorganic & Medicinal Chemistry
Mohamed A IsmailDavid W Boykin

Abstract

A series of biphenyl benzimidazoles diamidines 6a-i were synthesized from their respective diamidoximes, through the bis-O-acetoxyamidoxime followed by hydrogenation in glacial acetic acid/ethanol in the presence of Pd-C. The target compounds contain hydroxy and/or methoxy substituted 1,3-phenyl groups as the central spacer between the two amidino bearing aryl groups. All of the diamidines showed strong DNA affinities as judged by high DeltaTm values with poly(dA.dT)2, which varied with structure and is discussed. Seven of the nine new diamidines gave in vitro IC50 values of approximately 30 nM or less versus Trypanosoma brucei rhodesiense (T.b.r.). Generally the diamidines were less active versus Plasmodium falciparum (P.f.), however one compound exhibited excellent activity with an IC50 value of 2.1 nM. Five of the nine diamidines exhibited excellent in vivo activity in the trypanosomal STIB900 mouse model giving 3/4 or 4/4 cures at dosage of 20 mg/kg i.p. and three showed similar efficacy at dosage of 10 mg/kg or lower.

Citations

Dec 18, 2013·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Y Shyma MaryIlkay Yildiz
Feb 15, 2014·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Y Shyma MaryIlkay Yildiz
Jun 2, 2011·Journal of the American Chemical Society·Yang LiuW David Wilson
Jun 26, 2013·Journal of Medicinal Chemistry·Donald A PatrickRichard R Tidwell
Nov 26, 2009·Journal of Medicinal Chemistry·Stanislav A BakunovRichard R Tidwell
Oct 16, 2010·Organic & Biomolecular Chemistry·Padraic S NagleIsabel Rozas
Sep 30, 2009·Antimicrobial Agents and Chemotherapy·Kirsten GillingwaterReto Brun
Jul 30, 2005·Expert Opinion on Investigational Drugs·Dietmar Steverding, Kevin M Tyler
Oct 30, 2014·Chemical Biology & Drug Design·Rangappa S KeriBhari Mallanna Nagaraja
Mar 19, 2008·Basic & Clinical Pharmacology & Toxicology·Anja BürenheideBernd Clement
Jun 24, 2015·Journal of Chemical Biology·Biswadip Banerji, Sumit Kumar Pramanik
Oct 26, 2007·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Marijana Hranjec, Grace Karminski-Zamola
Jun 3, 2016·Dalton Transactions : an International Journal of Inorganic Chemistry·Daniel A ZuritaJuventino J García
Oct 11, 2011·ChemMedChem·Joscha KotthausBernd Clement
May 25, 2016·Antimicrobial Agents and Chemotherapy·M R Simões-SilvaM N C Soeiro
Nov 17, 2006·Nature Chemical Biology·Adam R Renslo, James H McKerrow
May 1, 2019·Medicinal Chemistry·Smita VermaS J S Flora
Apr 23, 2020·Antibiotics·Ayaz AnwarNaveed Ahmed Khan
Oct 10, 2008·Journal of Medicinal Chemistry·Stanislav A BakunovRichard R Tidwell
Mar 10, 2009·Journal of Medicinal Chemistry·Svetlana M BakunovaRichard R Tidwell
Jul 18, 2009·Journal of Medicinal Chemistry·Svetlana M BakunovaRichard R Tidwell
Oct 18, 2014·ACS Chemical Biology·Mateo I SánchezM Eugenio Vázquez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Anthelmintics

Anthelmintics or antihelminthics are a group of antiparasitic drugs that expel parasitic worms (helminths) and other internal parasites from the body by either stunning or killing them and without causing significant damage to the host. Discover the latest research on anthelmintics here.

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.