In vitro antitumor and antimicrobial activities of N-substituents of maleimide by adamantane and diamantane.
New N-1-adamantylcitraconimide (compound 1) and N-1-diamantylcitraconimide (compound 2) were synthesized by reaction of citraconic anhydride with 1-aminoadamantane, and 1-aminodiamantane, respectively, followed by imidization with acetic anhydride and sodium acetate. Compound 1, N-1-adamantylmaleimide (compound 3) and N-1-diamantylmaleimide (compound 4) exhibited strong growth-inhibitory activity against four cancer cell lines (Colo 205, Hep G2, SK-BR-3 and Molt-4). Moreover, compound 1 showed relatively specific cytotoxicity against the test tumor cell lines. Compound 2 exhibited growth inhibitory activity against Colo 205, and SK-BR-3 cells, similar to 5-fluorouracil. It was noted that compound 2 showed relatively low cytotoxicity against Molt-4 cells, approximately 42 times lower than 5-fluorouracil. The N-substituents of imides with adamantly substituents have a more potent antitumor activity than the imides with diamantyl substituents. The imides with methyl substituents (compounds 1 and 2) showed relatively higher selectivity against the tested cancer cell lines than the imides without methyl substituents (compounds 3 and 4). Compounds 3 and 4 show good in vitro activities against Staphylococcus aureus and Trichophyton mentagrophytes. Compound 1 had weak antimicrobial activity against T. mentagrophytes.
Wang
J J
JJ
Institute of Pharmacology, National Yang-Ming University, National Taipei College of Nursing, Taiwan.
Wang
S S
SS
Lee
C F
CF
Chung
M A
MA
Chern
Y T
YT
D000218:Adamantane / Q000737:chemistry / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004926:Escherichia coli / Q000187:drug effects; D008301:Maleimides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D009161:Mycobacterium / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D008301:Maleimides; D000218:Adamantane