title: Potent antiprotozoal activity of a novel semi-synthetic berberine derivative.
abstract: Treatment of diseases such as African sleeping sickness and leishmaniasis often depends on relatively expensive or toxic drugs, and resistance to current chemotherapeutics is an issue in treating these diseases and malaria. In this study, a new semi-synthetic berberine analogue, 5,6-didehydro-8,8-diethyl-13-oxodihydroberberine chloride (1), showed nanomolar level potency against in vitro models of leishmaniasis, malaria, and trypanosomiasis as well as activity in an in vivo visceral leishmaniasis model. Since the synthetic starting material, berberine hemisulfate, is inexpensive, 8,8-dialkyl-substituted analogues of berberine may lead to a new class of affordable antiprotozoal compounds.
authors.affiliation: College of Pharmacy, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Bahar
authors.forename: Ye
authors.initials: Y
authors.lastname: Deng
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhu
authors.forename: Shanshan
authors.initials: S
authors.lastname: He
authors.forename: Trupti
authors.initials: T
authors.lastname: Pandharkar
authors.forename: Mark E
authors.initials: ME
authors.lastname: Drew
authors.forename: Armando
authors.initials: A
authors.lastname: Navarro-Vázquez
authors.forename: Clemens
authors.initials: C
authors.lastname: Anklin
authors.forename: Roberto R
authors.initials: RR
authors.lastname: Gil
authors.forename: Raymond W
authors.initials: RW
authors.lastname: Doskotch
authors.forename: Karl A
authors.initials: KA
authors.lastname: Werbovetz
authors.forename: A Douglas
authors.initials: AD
authors.lastname: Kinghorn
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001599:Berberine / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects; D007896:Leishmaniasis / Q000188:drug therapy; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008958:Models, Molecular; D010271:Parasites / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects; D011528:Protozoan Infections / Q000188:drug therapy*; D014346:Trypanosoma brucei brucei / Q000187:drug effects; D014352:Trypanosomiasis / Q000188:drug therapy; D014709:Vero Cells
chemical_list: D000981:Antiprotozoal Agents; D001599:Berberine