Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines.
The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative 1h shows high potency in both antiviral and antitumor models.
Van Maarseveen
J H
JH
Department of Organic Chemistry, University of Nijmegen, The Netherlands.
Hermkens
P H
PH
De Clercq
E
E
Balzarini
J
J
Scheeren
H W
HW
Kruse
C G
CG
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006678:HIV / Q000187:drug effects; D006801:Humans; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D018139:Simplexvirus / Q000187:drug effects; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014561:Urochordata
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D002243:Carbolines