Design, synthesis and biological evaluation of tasiamide analogues as tumor inhibitors.
Eighteen analogues of the marine cytotoxic linear peptide tasiamide were designed, synthesized and screened for their inhibitory activities against the growth of human nasopharyngeal carcinoma (KB) and human non-small cell lung tumor (A549) cell lines. The results indicated that minor modifications of the C-terminus with aromatic groups were tolerated, with the IC₅₀ values between 1.29 and 12.88 μM against these two cancer cell lines. Truncation, minor modifications at the N-terminus or elimination of the N-methyl groups in N-Me-D-Gln and/or N-Me-D-Phe residues resulted in inactive analogues.
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. zhangw416@fudan.edu.cn.
Wei
W
Zhang
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. tiantiansunchina@gmail.com.
Tiantian
T
Sun
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. zhenhua_ma2@163.com.
Zhenhua
Z
Ma
Department of Medicinal Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China. liyx417@fudan.edu.cn.
Yingxia
Y
Li
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002277:Carcinoma; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D006801:Humans; D020128:Inhibitory Concentration 50; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009842:Oligopeptides; C470799:tasiamide