title: Mefloquine-oxazolidine derivatives: a new class of anticancer agents.
abstract: A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines, derived from (R*, S*)-(±)-mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 μg/mL. In general compounds with aryl groups having strong electron-releasing substituents, such as HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are active. However, other factors such as steric effects may play a role. As both the active and non-active conformations of the mefloquine-oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.
authors: Laboratório de Oncologia Experimental, Universidade Federal do Ceará, Fortaleza, CE 3157, Brazil.
authors: Felipe A R
authors: FA
authors: Rodrigues
authors: Igor da S
authors: Ida S
authors: Bomfim
authors: Bruno C
authors: BC
authors: Cavalcanti
authors: Claudia
authors: C
authors: Pessoa
authors: Raoni S B
authors: RS
authors: Goncalves
authors: James L
authors: JL
authors: Wardell
authors: Solange M S V
authors: SM
authors: Wardell
authors: Marcus V N
authors: MV
authors: de Souza
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015767:Mefloquine / Q000737:chemistry*; D008968:Molecular Conformation; D010080:Oxazoles / Q000737:chemistry*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D010080:Oxazoles; D011804:Quinolines; C064210:oxazolidine; D015767:Mefloquine
keywords: anticancer; antitumor activity; mefloquine; oxazolidine