| Title | Synthesis and cytotoxic activities of beta-carboline amino acid ester conjugates |
| Authors | Zhao, Ming Bi, Lanrong Wang, Wei Wang, Chao Baudy-Floc'h, Michele Ju, Jingfang Peng, Shiqi |
| Affiliation | Univ S Alabama, Mitchell Canc Inst, Mobile, AL 36688 USA. Capital Univ Med Sci, Coll Pharmaceut Sci, Beijing 100054, Peoples R China. Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China. Univ Rennes 1, CNRS, UMR 6226, Grp Ciblage & Autoassemblages Fonct, F-35042 Rennes, France. Univ S Alabama, Mitchell Canc Inst, 307 N Univ Blvd, Mobile, AL 36688 USA. |
| Keywords | beta-carboline cytotoxicity anti-cancer PROTEIN-DNA INTERACTIONS THYMIDYLATE SYNTHASE ANTITUMOR AGENTS INTESTINAL-ABSORPTION ANTINEOPLASTIC AGENTS PEPTIDE TRANSPORTER BIOLOGICAL-ACTIVITY ANTICANCER AGENTS DRUG TRANSPORT MESSENGER-RNA |
| Issue Date | 2006 |
| Publisher | 生物有机化学与医药化学 |
| Citation | BIOORGANIC & MEDICINAL CHEMISTRY.2006,14,(20),6998-7010. |
| Abstract | beta-Carboline represents a class of compounds with potent anti-tumor activity by intercalating with DNA. To further enhance the cytotoxic potency and bioavailability of beta-carboline, a series of novel beta-carboline amino acid ester conjugates were designed and synthesized, and the cytotoxic activities of these compounds were tested using a panel of human tumor cell lines. In addition, the membrane permeability of these compounds was evaluated in vitro using a Caco-2 cell monolayer model. The P-carboline amino acid ester conjugates demonstrated improved cytotoxic activity compared to the parental beta-carbolines. In particular, the Lys/Arg conjugates were the most potent analogs with an IC50 value of 4 and 1 mu M against human cervical carcinoma cells. The low interaction energy of Arg conjugate based on molecular modeling may contribute to its enhanced cytotoxicity. Taken together, this study provided new insights into structure-activity relationships in the beta-carboline amino acid ester conjugates and identified the beta-carboline Lys/Arg conjugates as promising lead compounds for further in vivo biological and molecular evaluation. (c) 2006 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/251367 |
| ISSN | 0968-0896 |
| DOI | 10.1016/j.bmc.2006.06.021 |
| Indexed | SCI(E) |
| Appears in Collections: | 药学院 |
