Design and synthesis of glycoside inhibitors of glioma and melanoma growth.
An N-acetylglucosaminide derivative with a pentaerythritol substituent at position C-6 was previously synthesized and shown to inhibit neural tumor growth. Now, we report the preparation of a series of new synthetic compounds introducing systematic changes in the nature, polarity, and size of the sugar substituents. The antimitotic activity of the new compounds was tested on cultured rat (C6) and human (U-373) glioma lines and on a human melanoma line (A-375). The antimitotic and antitumoral activity of the new compounds on glioma cell lines increased up to 2 orders of magnitude with respect to the parent compound or was abolished, permitting a detailed structure-function analysis of the new antitumorals. One of the glycosides inhibited melanoma division with an ID50 below the micromolar range.
García-Alvarez
Isabel
I
Instituto de Química OrgAnica General, CSIC, Juan de la Cierva 3, 28006 Madrid, Spain.
Corrales
Guillermo
G
Doncel-Pérez
Ernesto
E
Muñoz
Ana
A
Nieto-Sampedro
Manuel
M
Fernández-Mayoralas
Alfonso
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005910:Glioma; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008545:Melanoma; D051381:Rats; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D006027:Glycosides