title: Novel hybrid DHPM-fatty acids: synthesis and activity against glioma cell growth in vitro.
abstract: We described the first synthesis of fatty acid 3,4-dihydropyrimidinones (DHPM-fatty acids) using the Biginelli multicomponent reaction. Antiproliferative activity on two glioma cell lines (C6 rat and U-138-MG human) was also reported. The novel DHPM-fatty acids reduced glioma cell viability relative to temozolomide. Hybrid oxo-monastrol-palmitic acid was the most potent, reducing U-138-MG human cell viability by ca. 50% at 10 μM. In addition, the DHPM-fatty acids showed a large safety range to neural cells, represented by the organotypic hippocampal culture. These results suggest that the increased lipophilicity of DHPM-fatty acids offer a promising approach to overcoming resistance to chemotherapy and may play an important role in the development of new antitumor drugs.
authors: Laboratório Kolbe de Síntese Orgânica, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil.
authors: Tamara G M
authors: TG
authors: Treptow
authors: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Fabrício
authors: F
authors: Figueiró
authors: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Elisa H F
authors: EH
authors: Jandrey
authors: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Ana M O
authors: AM
authors: Battastini
authors: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Christianne G
authors: CG
authors: Salbego
authors: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Juliana B
authors: JB
authors: Hoppe
authors: Laboratório Kolbe de Síntese Orgânica, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil.
authors: Priscila S
authors: PS
authors: Taborda
authors: Laboratório Kolbe de Síntese Orgânica, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil.
authors: Sabrina B
authors: SB
authors: Rosa
authors: Laboratório Kolbe de Síntese Orgânica, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil.
authors: Luciana A
authors: LA
authors: Piovesan
authors: Laboratório de Síntese Orgânica, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Caroline Da R
authors: Cda R
authors: Montes D'Oca
authors: Laboratório de Síntese Orgânica, Universidade Federal do Rio Grande do Sul, UFRGS, Porto Alegre, RS, Brazil.
authors: Dennis
authors: D
authors: Russowsky
authors: Laboratório Kolbe de Síntese Orgânica, Universidade Federal do Rio Grande, FURG, Rio Grande, RS, Brazil. Electronic address: dqmdoca@furg.br.
authors: Marcelo G
authors: MG
authors: Montes D'Oca
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005227:Fatty Acids; C010922:5,6-dihydrouridine; D014529:Uridine
keywords: Antiproliferative activity; Fatty acids; Glioma cell; Monastrol; Oil chemistry