title: In pursuit of natural product leads: synthesis and biological evaluation of 2-[3-hydroxy-2-[(3-hydroxypyridine-2-carbonyl)amino]phenyl]benzoxazole-4-carboxylic acid (A-33853) and its analogues: discovery of N-(2-benzoxazol-2-ylphenyl)benzamides as novel antileishmanial chemotypes.
abstract: The first synthesis and biological evaluation of antibiotic 31 (A-33853) and its analogues are reported. Initial screening for inhibition of L. donovani, T. b. rhodesiense, T. cruzi, and P. falciparum cultures followed by determination of IC(50) in L. donovani and cytotoxicity on L6 cells revealed 31 to be 3-fold more active than miltefosine, a known antileishmanial drug. Compounds 14, 15, and 25 selectively inhibited L. donovani at nanomolar concentrations and showed much lower cytotoxicity.
authors.affiliation: Drug Discovery Program, Department of Medicinal Chemistry and Pharmacognosy, University of Illinois at Chicago, 833 S. Wood Street, Chicago, Illinois 60612, USA.
authors.forename: Suresh K
authors.initials: SK
authors.lastname: Tipparaju
authors.forename: Sipak
authors.initials: S
authors.lastname: Joyasawal
authors.forename: Marco
authors.initials: M
authors.lastname: Pieroni
authors.forename: Marcel
authors.initials: M
authors.lastname: Kaiser
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Alan P
authors.initials: AP
authors.lastname: Kozikowski
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001685:Biological Factors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D013237:Stereoisomerism
chemical_list: D000981:Antiprotozoal Agents; D001549:Benzamides; D001583:Benzoxazoles; D001685:Biological Factors; C041570:A 33853