Synthesis and in-vitro antitumor activities of some mannich bases of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones.
A novel series of 2-substituted aminomethyl-9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 5a-q was synthesized via aminomethylation of 9-alkyl-1,2,3,4-tetrahydrocarbazole-1-ones 4a-e with hydrochlorides of the respective amines 6a-m. The structures of these newly synthesized compounds were characterized by (1)H-NMR, MS, and elemental analysis. All the compounds were tested for their cytotoxic activity in vitro against four human tumor cell lines including human non-small lung cancer cells (A549), human gastric adenocarcinoma (SGC), human colon cancer cell (HCT116), human myeoloid leukemia cells (K562), and one multi-drug resistant subline (KB-VCR). Most compounds showed moderate to potent cytotoxic activity against the tested cell lines. Preliminary mechanism research indicated that the most promising compound, 2-diethylaminomethyl-9-methyl-1,2,3,4-tetrahydrocarbazole-1-one 5c, exhibited a potential inhibitory effect against microtubule.
Chen
Jing
J
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
Lou
Jianshu
J
Liu
Tao
T
Wu
Ru
R
Dong
Xiaowu
X
He
Qiaojun
Q
Yang
Bo
B
Hu
Yongzhou
Y
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008352:Mannich Bases / Q000138:chemical synthesis / Q000494:pharmacology; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure
D000970:Antineoplastic Agents; D002227:Carbazoles; D008352:Mannich Bases; C409925:1,2,3,4-tetrahydrocarbazole