title: Oxazolo[3,2-a]pyridine. A new structural scaffold for the reversal of multi-drug resistance in Leishmania.
abstract: Compounds belonging to three different classes of fused heterocyclic systems, structurally related to Calcium-channel blockers of the 1,4-dihydropyridine family, were evaluated in their ability to overcome leishmanial resistance to common drugs in a MDR Leishmania tropica strain. Compounds with the skeletal basis of oxazolo[3,2-a]pyridine displayed significant reversion of resistance to daunomycin and miltefosine, with reversion indexes up to 6.7-fold and 8.7-fold, respectively. Most interestingly, the enantiopure compound 20S attained to revert the resistance to both drugs and fairly more significantly than its enantiomer 20R.
authors.affiliation: Departamento de Química Farmacéutica, Facultad de Farmacia, CIETUS, IBSAL, Universidad de Salamanca, 37007-Salamanca, Spain. escab@usal.es
authors.forename: Esther
authors.initials: E
authors.lastname: Caballero
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Manzano
authors.forename: Pilar
authors.initials: P
authors.lastname: Puebla
authors.forename: Santiago
authors.initials: S
authors.lastname: Castanys
authors.forename: Francisco
authors.initials: F
authors.lastname: Gamarro
authors.forename: Arturo
authors.initials: A
authors.lastname: San Feliciano
mesh_terms: D000981:Antiprotozoal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D007895:Leishmania tropica / Q000187:drug effects*; D015394:Molecular Structure; D010080:Oxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D010080:Oxazoles; D011725:Pyridines; C577918:oxazolo(3,2-a)pyridine