The Synthesis of Derivatives of 1-Substituted Isoquinolines and Their Biological Activity
| Autor: | Chen-Yuan Kuo, 郭振源 |
|---|---|
| Rok vydání: | 2006 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 94 Isoquinoline alkaloids are interested due to their widespread occurrence in nature and broad biological effects. A series of 1-(2-nitro phenyl)-3,4-dihydroisoquinolines were reduced under very mild reaction conditions in the presence of Tin(Ⅱ) chloride dihydrate (SnCl2.2H2O) to give 5,6-dihydroindazolo[3,2-a]isoquinolines 4a-i. A mechanism for this reaction is proposed and their antitumor activity was evaluated. Besides, phenoxyalkylamino moiety is known to be the mother structure of α-blockers and many benzylisoquimoline- based alkaloids exhibitd excellent antagonistic activity on Ca+2-channel. In this dissertation, thirteen new N-phenoxyethyl -1-(substituted)isoquinolines (6a-c, 6f, 6p, 7a-c, 7f) were synthesized by treatment of 1,2,3,4-THIQs (5a-c, 5f, 5p) with 1-bromo-2-phenoxyethane. Their α-blocking activity will be tested. On the other hand, fifteen cis-dichloroplatinum complexes (8a-8o) were synthesized by treatment of 1-(2-aminophenyl)-1,2,3,4-THIQs (5a-5o) with K2PtCl4. The antitumor activity of these compounds was examined against four different human tumor cell lines. Their structure-activity relationships for antitumor activity were reported. All of these compounds exhibited activity against MCF-7 cell line and showed good activity against WiDr cell line except 8c and 8f. On the other hand, compounds 8j and 8o are more active than the other compounds against Hepa59T/VGH cell line. The electron-donating group at the 6-position of isoquinoline ring seems to decrease the antitumor activity and the chloro substituent at the C-4 position of the aniline ring shown the highest potency. The “trans influence” dominates the control of the stability of [1-(2-aminophenyl)-1,2,3,4- THIQ]dichloroplatinums(Ⅱ). |
| Databáze: | Networked Digital Library of Theses & Dissertations |
| Externí odkaz: |
|