New antitumoral agents I: In vitro anticancer activity and in vivo acute toxicity of synthetic 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one and derivatives.
This paper describes a new method for the preparation of 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one 1 and its derivatives 2-5. This set of synthetic compounds exhibited high antitumoral activities regarding in vitro screening against several human tumor cell lines as lung carcinoma NCI-460, melanoma UACC-62, breast MCF-7, colon HT-29, renal 786-O, ovarian OVCAR-03 and ovarian expressing the resistance phenotype for adriamycin NCI-ADR/RES, prostate PC-3, and leukemia K-562. Compounds were also tested against murine tumor cell line B16F10 melanoma and lymphocytic leukemia L1210 as well as to their effect toward normal macrophages. Specific activity against colon cancer cells HT-29 was observed for all tested compounds and suggests further studies with models of colon cancer. Compounds 1, 2, and 4 showed significant cytotoxic activity with IC(50) values 2.3 microM for all human cancer cell lines. Intraperitoneal acute administration of compound 1 and 2 showed very low toxicity rate.
Quincoces Suarez
José Agustín
JA
Laboratory of Organic Synthesis, Universidade Bandeirante de São Paulo (UNIBAN), São Paulo, Brazil. quinco99@hotmail.com
Rando
Daniela Gonçales
DG
Santos
Reginaldo Pereira
RP
Gonçalves
Carolina Passarelli
CP
Ferreira
Elizabeth
E
de Carvalho
João Ernesto
JE
Kohn
Luciana
L
Maria
Durvanei Augusto
DA
Faião-Flores
Fernanda
F
Michalik
Dirk
D
Marcucci
Maria Cristina
MC
Vogel
Christian
C
D000818:Animals; D000840:Anisoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D013329:Structure-Activity Relationship
C543314:1,5-bis(4-acetoxy-3-methoxyphenyl)-1,4-pentadien-3-one; D000840:Anisoles; D000970:Antineoplastic Agents; D007659:Ketones