Synthesis and in vitro biological evaluation of hybrids from tetrahydro-β-carboline and hydroxylcinnamic acid as antitumor carcinoma agents.
Novel hybrids 8a-j and 9a-j were designed and synthesized by coupling the carboxyl group of hydroxylcinnamic acids with tetrahydro-β-carboline alkaloids which were linked with different substituted nitrogen-containing heterocycles at the positions-N9, and their in vitro biological activities were evaluated. It was found that most hybrids showed good to moderate anti-tumor activities. Especially, compound 9j had a great potency superior to 5-fluorouracil (5-FU) and comparable to adriamycin in human cancer cells, and could selectively inhibit tumor cells, but not inhibit non-tumor cell proliferation in vitro. More importantly, apoptosis assay indicated that 9j could significantly induce tumor cell apoptosis in a dose-dependent manner. Therefore, our novel findings may provide a new framework for the design of new hybrids for the intervention of human cancers.
Department of Hematology and Oncology, The Second Affiliated Hospital, Wenzhou Medical University.
Ying
Y
Lin
Xuanping
X
Xia
Rongxin
R
Yao
Li
L
Ni
Jie
J
Hu
Wenjian
W
Guo
Baoling
B
Zhu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002243:Carbolines / Q000737:chemistry*; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D002934:Cinnamates / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002243:Carbolines; D002934:Cinnamates; C029010:cinnamic acid; C009804:tryptoline; D005472:Fluorouracil