Synthesis and antitumour activity of the Primin (2-methoxy-6-n-pentyl-1,4-benzoquinone) and analogues.
Cancer is a serious worldwide health threat, killing almost seven million people per year. Quinones are an important class of antitumour agents that are activated by tumour hypoxia. Primin (2-methoxy-6-n-pentyl-1,4-benzo-quinone), a naturally-occurring product obtained from Primula obconica (Primulaceae) has shown antimicrobial and antitumour properties. The synthesis of the Primin to obtain 3-, 5- or 6-alkyl substituted derivatives has been previously attempted seeking antitumour activity. The intermediate reaction products, 2-methoxy-hydroquinone-di-(2'-tetrahydro-pyranyl) ether and 2-methoxy-6-n-pentyl-hydroquinone-di-(2'-tetrahydropyranyl) ether were obtained and evaluated against sarcoma 180 (S-180) and Ehrlich carcinoma, as well as toxicity tests were performed. The antitumour activity tests showed that these intermediate compounds were able to inhibit S-180 sarcoma and Ehrlich carcinoma growth in mice. These results indicated that the tetrahydropyranyl protect group conserved the antitumour activity in comparison with quinone group, however, it exhibited a less toxic effect, with no characteristic of quinones. These results can suggest that compound 2-methoxy-6-n-pentyl-hydroquinone-di-(2'-tetrahydropyranyl) ether may act as a prodrug with some advantages in comparison with the Primin.
Brondani
D J
DJ
Laboratório de Planejamento, Avaliação e Síntese de Fármacos, LABSINFA, Departamento de Ciências Farmacêuticas, Universidade Federal de Pernambuco, Pernambuco, Brazil.
Nascimento
C R M
CR
de M Moreira
D R
DR
Lima Leite
A C
AC
de Souza
I A
IA
Bieber
L W
LW
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D016227:Benzoquinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D013997:Time Factors
D000970:Antineoplastic Agents; D016227:Benzoquinones; C014773:primin