Full text
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| Author(s): |
Vanessa Caixeta Pereira
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Química |
| Defense date: | 2011-12-08 |
| Examining board members: |
Ronaldo Aloise Pilli;
Carlos Alberto Montanari;
Wanda Pereira Almeida
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| Advisor: | Ronaldo Aloise Pilli |
| Abstract | |
Goniothalamin (9), a natural product isolated from several plants of the Goniothalamus genus, has been highlighted in the literature for presenting good potency against human tumor cell lines in in vitro assays, as well as good results in in vivo models. This makes goniothalamin a promising model for designing new compounds. Herein, we propose the synthesis and the cytotoxic evaluation of two classes of goniothalamin derivatives. The first class comprises derivatives with substituents at position 4 of the 5,6-di-hydropyran-2-one moiety. Alkyl and acyl derivatives (17,24-28) were obtained from kavalactone (23) after well-known alkylation and acylation reaction in bad to good yields. Kavalactone (23) was obtained from cinnamaldehyde (10) and ethyl acetoacetate (29) via an aldol reaction followed by in situ lactonization, in 15% yield. The antiproliferative assay showed that none of these derivatives was more cytotoxic than goniothalamin and none presented selectivity for tumor cell lines. The second class of compounds presents the substitution of the lactone by a lactam moiety. Lactam derivatives 46 - 51 were synthesized in 3 steps and overall yields ranging from 18 to 60%. The first step was the imine formation from the respective aldehyde (10,52-56) followed by allylmagnesium bromide addition to form primary amine 57. This was reacted with acryloyl or crotonoyl chloride to generate amide 58. Finally, the desired lactam was obtained by treating amide 58 with 6 mol% of Grubbs¿ second generation catalyst. The in vitro antiproliferative evaluation showed that 9 was more cytotoxic than the derivatives. However, derivative 49 presented selectivity for two tumor cell lines PC-03 (prostate) and K562 (leukemia) (AU) | |
| FAPESP's process: | 09/04627-2 - Synthesis and biological evaluation of phosphates, hosphoramides and carbamate derived from dihydropyranones |
| Grantee: | Vanêssa Caixeta Pereira |
| Support Opportunities: | Scholarships in Brazil - Master |