TY - JOUR
T1 - Study on synthesis of thalidomide analogues and their bioactivities; Inhibition on iNOS pathway and cytotoxic effects
AU - Yeh, Chao Bin
AU - Lin, Pen Yuan
AU - Hwang, Jin Ming
AU - Su, Chi Jung
AU - Yeh, Ying Tung
AU - Yang, Shun Fa
AU - Chou, Ming Chih
N1 - Funding Information:
Acknowledgments We would like to thank Professor Jer-Yuh Liu from the Graduate Institute of Cancer Biology, College of Medicine, China Medical University for his consultation and invaluable advice on this paper. This study was supported by a research grant from Chung Shan Medical University Hospital, Taiwan (CSH-2011-C-001).
PY - 2012/7
Y1 - 2012/7
N2 - Synthetic thalidomide analogues (compounds 1-35), including phenylphthalimide, pyridylphthalimide, aminobenzylphthalimide, and diphenylazophthalimide, were tested for their cytotoxic effects on human cancer cell lines Hep2 (Human Larynx Carcinoma Cells), HL-60 (Human Myeloid Leukemia Cells), NUGC (Human Gastric Carcinoma Cells), and HONE-1 (Human Nasopharyngeal Carcinoma Cells) because the incidence rate is more prominent in Asian countries than in Western countries. Compounds 17, 27, 28, and 35 were found to have antitumor activity in Hep2 and HL-60 cell lines. Compounds 2, 4, 15, 17, 19, 20, 23, and 27 can inhibit nitric oxide (NO) synthase activity by more than 90%. These thalidomide analogues were found to be potent inducible nitric oxide synthase (iNOS) inhibitors, and the iNOS inhibiting potential of compounds 17 and 27 might be an advantage for anticancer therapy. In conclusion, inhibition of NO synthesis is a new development in cancer therapy for now and in the future. We modified the structures of the thalidomide analogues to have a stronger anticancer effect and a good therapeutic effect.
AB - Synthetic thalidomide analogues (compounds 1-35), including phenylphthalimide, pyridylphthalimide, aminobenzylphthalimide, and diphenylazophthalimide, were tested for their cytotoxic effects on human cancer cell lines Hep2 (Human Larynx Carcinoma Cells), HL-60 (Human Myeloid Leukemia Cells), NUGC (Human Gastric Carcinoma Cells), and HONE-1 (Human Nasopharyngeal Carcinoma Cells) because the incidence rate is more prominent in Asian countries than in Western countries. Compounds 17, 27, 28, and 35 were found to have antitumor activity in Hep2 and HL-60 cell lines. Compounds 2, 4, 15, 17, 19, 20, 23, and 27 can inhibit nitric oxide (NO) synthase activity by more than 90%. These thalidomide analogues were found to be potent inducible nitric oxide synthase (iNOS) inhibitors, and the iNOS inhibiting potential of compounds 17 and 27 might be an advantage for anticancer therapy. In conclusion, inhibition of NO synthesis is a new development in cancer therapy for now and in the future. We modified the structures of the thalidomide analogues to have a stronger anticancer effect and a good therapeutic effect.
KW - Nitric oxide synthase inhibitors
KW - Thalidomide
KW - Thalidomide analogues
UR - http://www.scopus.com/inward/record.url?scp=84861860275&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861860275&partnerID=8YFLogxK
U2 - 10.1007/s00044-011-9603-7
DO - 10.1007/s00044-011-9603-7
M3 - Article
AN - SCOPUS:84861860275
SN - 1054-2523
VL - 21
SP - 953
EP - 963
JO - Medicinal Chemistry Research
JF - Medicinal Chemistry Research
IS - 7
ER -
