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Enantioselective semisynthesis of novel cephalotaxine esters with potent antineoplastic activities against leukemia.
Yang, Yujian; Yu, Qiuchun; Hu, Lean; Dai, Botao; Qi, Ruxi; Chang, Yu; Zhang, Qingwen; Zhang, Zhang; Li, Yingjun; Zhang, Xumu.
Afiliação
  • Yang Y; Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518000, China.
  • Yu Q; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou, 510632, China.
  • Hu L; Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518000, China.
  • Dai B; Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518000, China.
  • Qi R; Cryo-EM Center, Southern University of Science and Technology, Shenzhen, 518055, China.
  • Chang Y; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou, 510632, China.
  • Zhang Q; State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macao SAR, 999078, China. Electronic address: qwzhang@um.edu.mo.
  • Zhang Z; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou, 510632, China. Electronic
  • Li Y; Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518000, China. Electronic address: liyj@sustech.edu.cn.
  • Zhang X; Academy for Advanced Interdisciplinary Studies, Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Department of Chemistry, and Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518000, China; Shenzhen Bay Laboratory, Shenzhen, 518132, China. Electronic a
Eur J Med Chem ; 244: 114731, 2022 Dec 15.
Article em En | MEDLINE | ID: mdl-36242991
Cephalotaxine-type alkaloids (CTAs), represented by homoharringtonine (HHT, 1), display potent efficacy against different types of leukemia cells. In this study, a method for hydrogenation of ß-substituted itaconic acid monoesters with chiral Ru[DTBM-SegPhos](OAc)2 was developed. This metal-catalyzed asymmetric hydrogenation enabled the convenient semisynthesis of novel cephalotaxine derivatives with chiral 2'-substituted-succinic acid 4-mono-methyl esters as side chains. The preliminary structure-activity relationship (SAR) of the compounds' antineoplastic activities was studied. Eventually, we discovered compound 10b with potent antineoplastic activities against leukemia and broadly anticancer activities against a panel of cancer cells. Our study provided a highly enantioselective process enabling the semisynthesis of cephalotaxine derivatives, which are interesting for further study on a scientific basis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia / Harringtoninas / Antineoplásicos Limite: Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China
Texto completo
Imprimir
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Leucemia / Harringtoninas / Antineoplásicos Limite: Humans Idioma: En Revista: Eur J Med Chem Ano de publicação: 2022 Tipo de documento: Article País de afiliação: China