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Design and Synthesis of Biotinylated Bivalent Carboline Derivatives as Potent Antitumor Agents. 2020
Xueyuan Chen, and
Yi Zheng, and
Songlin Song, and
Ying Liu, and
Yi Wang, and
Yong Huang, and
Xiaoyi Zhang, and
Meng Zhang, and
Ming Zhao, and
Yuji Wang, and
Li Li
Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, School of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, P. R. China.
Compound 6, a novel β-carboline comprising two 1-methyl-9H-β-carboline-3-carboxylic acids and a biotin moiety conjugated together using tris(2-aminoethyl)amine, was synthesized and tested for its cytotoxicity toward MCF-7 and HepG2 cell lines and antitumor potency in an S180 tumor-bearing mouse model. Compound 6 was delivered via biotin receptor-mediated endocytosis and exerted its therapeutic effects by intercalation binding with DNA. In vivo antitumor evaluations of 6 revealed that it is efficacious and exhibits low systemic toxicity.
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