Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents.
Novel (E)-1-aryl-3-(3-aryl-1-phenyl-1H-pyrazol-4-yl)prop-2-en-1-ones 5/6 (pyrazolic chalcones) were synthesized from a Claisen-Schmidt reaction of 3-aryl-1-phenylpyrazol-4-carboxaldehydes 4 with several acetophenone derivatives 1. Subsequently, the microwave-assisted cyclocondensation reaction of chalcones 5/6 with hydrazine afforded the new racemic 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazoles 7 or their N-acetyl derivatives 8 and 9 when reactions where carried out in DMF or acetic acid, respectively. Several of these compounds were screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where 5c and 9g showed remarkable activity mainly against leukemia (K-562 and SR), renal cancer (UO-31) and non-small cell lung cancer (HOP-92) cell lines, with the most important GI50 values ranging from 0.04 to 11.4 microM, from the in vitro assays.
Insuasty
Braulio
B
Heterocyclic Compounds Research Group, Department of Chemistry, Universidad del Valle, A. A. 25360, Cali, Colombia. brainsu@univalle.edu.co
Tigreros
Alexis
A
Orozco
Fabián
F
Quiroga
Jairo
J
Abonía
Rodrigo
R
Nogueras
Manuel
M
Sanchez
Adolfo
A
Cobo
Justo
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D045744:Cell Line, Tumor; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D007938:Leukemia / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D009369:Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D047188:Chalcones; D011720:Pyrazoles; C031280:pyrazole