Cytotoxicities, cell cycle and caspase evaluations of 1,6-diaryl-3(Z)-hexen-1,5-diynes, 2-(6-aryl-3(Z)-hexen-1,5-diynyl)anilines and their derivatives.
Compounds 3, 6-7, 9-10, 15-17, and 20-21 showed growth inhibition effects on a full panel of 60 human cancer cell lines, and most of the average IC50 values of the indicated analogues were from < 0.01 to 96.6 microM, in which analogues 16 and 17 revealed the highest cytotoxic activity with the cancer cell lines at 10(-7) M concentration range. During the cell cycle analysis, a moderate to high apoptotic progress induction was shown by 3, 9, 16-17, and 20 compared with the control, which 2-(6-(2-thienyl)-3(Z)-hexen-1,5-diynyl)aniline 16 showed the highest apoptotic effect. Structures 16-17 displayed a significant G2/M phase arrest in the cell growth cycle compared with other derivatives, which the proportions of the G2/M phase cells were accumulated to 71.5% and 82.6%, respectively. Moreover, the colorimetric assay of 16-17 also provided advanced evidence to the relationship between the compounds and the caspase-3 enzyme, which was one of the major promoters of apoptotic effect.
Lin
Chi-Fong
CF
Department of Biological Science and Technology, Chung Hwa College of Medical Technology, Taiwan, Taiwan.
Lo
Yu-Hsiang
YH
Hsieh
Ming-Chu
MC
Chen
Yi-Hua
YH
Wang
Jeh-Jeng
JJ
Wu
Ming-Jung
MJ
D000480:Alkynes / Q000737:chemistry; D000814:Aniline Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D016195:G2 Phase / Q000187:drug effects*; D006801:Humans; D014407:Tumor Cells, Cultured
D000480:Alkynes; D000814:Aniline Compounds; D000970:Antineoplastic Agents; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases