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Synthesis of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines as potential antitumor and antifungal agents.
Ramírez, Juan; Svetaz, Laura; Quiroga, Jairo; Abonia, Rodrigo; Raimondi, Marcela; Zacchino, Susana; Insuasty, Braulio.
Afiliação
  • Ramírez J; Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia.
  • Svetaz L; Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
  • Quiroga J; Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia.
  • Abonia R; Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia.
  • Raimondi M; Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
  • Zacchino S; Área Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, Suipacha 531, 2000 Rosario, Argentina.
  • Insuasty B; Grupo de Investigación de Compuestos Heterocíclicos, Departamento de Química, Universidad del Valle, AA 25360 Cali, Colombia. Electronic address: braulio.insuasty@correounivalle.edu.co.
Eur J Med Chem ; 92: 866-75, 2015 Mar 06.
Article em En | MEDLINE | ID: mdl-25638570
A new series of novel thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines 6a-g and 7a-g were obtained with high regioselectivity from the reaction of triamino- or tetraaminopyrimidines 4 and 5 with α,ß-unsaturated carbonyl compounds 3a-g based on 2,4-dichlorothiazol-5-carbaldehyde 1. Twelve of the synthesized compounds were selected and tested by US National Cancer Institute (NCI) for their antitumor activity against 60 different human tumor cell lines. Compounds 7d and 7g showed important GI50 ranges of 1.28-2.98 µM and 0.35-2.78 µM respectively under in vitro assays. In addition, 6a-g and 7a-g were tested for antifungal properties against the clinical important fungi Candida albicans and Cryptococcus neoformans. Although these compounds showed moderate activities against C. albicans, the 2-amino derivatives 7a-g and mainly 7a and 7b, showed high activity against standardized and clinical isolates of C. neoformans with MIC50 = 7.8-31.2 µg/mL, MIC80 = 15.6-31.2 µg/mL and MIC100 = 15.6-62.5 µg/mL. In addition, since both compounds were fungicide rather than fungistatic these thiazole-based 8,9-dihydro-7H-pyrimido[4,5-b][1,4]diazepines appear as good candidates for further development not only as antifungal but also as antitumor drugs.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinas / Azepinas / Tiazóis / Antifúngicos / Antineoplásicos Limite: Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Colômbia País de publicação: França

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Pirimidinas / Azepinas / Tiazóis / Antifúngicos / Antineoplásicos Limite: Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Colômbia País de publicação: França