Enantiomeric trans ß-aryl-δ-iodo-γ-lactones derived from 2,5-dimethylbenzaldehyde induce apoptosis in canine lymphoma cell lines by downregulation of anti-apoptotic Bcl-2 family members Bcl-xL and Bcl-2.
Bioorg Med Chem Lett
; 28(7): 1171-1177, 2018 04 15.
Article
em En
| MEDLINE
| ID: mdl-29534928
ABSTRACT
For many years, studies focused on developing new natural or synthetic compounds with antineoplastic activity have attracted the attention of researchers. An interesting group of such compounds seem to be those with both lactone moiety and an aromatic ring which, in addition to antimicrobial or antiviral activity, also exhibit antitumor properties. The study shows antitumor activity of two enantiomeric trans isomers of 5-(1-iodoethyl)-4-(2',5'-dimethylphenyl)dihydrofuran-2-one. Our aim was to determine their antitumor activity manifested as an ability to induce apoptosis in selected canine cancer cell lines as well as to evaluate differences in their strength depending on the configuration of their stereogenic centers. The enantiomers (+)-(4R,5S,6R)-1 and (-)-(4S,5R,6S)-2 were found to induce classical caspase-dependent apoptosis through downregulation of the expression of anti-apoptotic proteins Bcl-xL and Bcl-2. Although the mechanism of apoptosis induction was the same for both enantiomers, they differed in their strength, as stronger antineoplastic activity in vitro was exhibited by isomer (+)-(4R,5S,6R)-1.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Benzaldeídos
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Regulação para Baixo
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Apoptose
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Proteínas Proto-Oncogênicas c-bcl-2
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Proteína bcl-X
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Lactonas
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Antineoplásicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article