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Chinese Journal of Organic Chemistry >

2020 , Vol. 40 >Issue 2: 536 - 540

DOI: https://doi.org/10.6023/cjoc201908015

Environment-Friendly Synthesis of Targeted Anticancer Drug N-(N'-Carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) and the Evaluation of Its Activity to Penetrate Blood-Brain Barrier

  • Zhang Chao ,
  • Liu Zhijun ,
  • Li Yanbing ,
  • He Yepu ,
  • Lin Xiaohong ,
  • Chen Heru
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  • a Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632;
    b Guangzhou PharmCherub Medical Sci. &Tech. Incorporated Corporation, Guangzhou 510663;
    c Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, Jinan University, Guangzhou 510632

Received date: 2019-08-10

  Revised date: 2019-09-21

  Online published: 2019-10-09

Supported by

Project supported by the Natural Science Foundation of Guangdong Province (No. 2018B030311020).

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Abstract

Anti-cancer drug N-(N'-carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) has been designed based on targeting strategy and a 3-step method has been developed for the synthesis of procarbazine (Pcb). Firstly, 4-methylbenaldehyde, as starting material, was transformed into N-isopropyl-4-methylbenzamide using dibromoisocyanuric acid (DBI). This compound was then directly oxidized to N-isopropyl-4-formylbenzamide by 2-iodoxybenzoic acid (IBX). A reductive amination reaction was then followed leading to Pcb. At last, Pcb was condensed with N-carbobenzoxyglycylproline resulting in Z-GP-Pcb. The overall yield was 49.9%. Furthermore, an in vitro blood-brain barrier (BBB) permeation assay (PAMPA-BBB) was set up to evaluate the permeation activity of Z-GP-Pcb. It was found that the permeation constant (Pe) was (19.22±4.25)×10-6 cm·s-1, which was more than that of the parent drug Pcb[(11.14±1.34))×10-6 cm·s-1]. This evidence suggests that Z-GP-Pcb possesses high activity to penetrate BBB.

Key words： drug synthesis; procarbazine; drug design; targeted anti-cancer; fibroblast activation protein-α

Cite this article

Zhang Chao , Liu Zhijun , Li Yanbing , He Yepu , Lin Xiaohong , Chen Heru . Environment-Friendly Synthesis of Targeted Anticancer Drug N-(N'-Carbobenzoxyglycylprolyl)procarbazine (Z-GP-Pcb) and the Evaluation of Its Activity to Penetrate Blood-Brain Barrier[J]. Chinese Journal of Organic Chemistry, 2020 , 40(2) : 536 -540 . DOI: 10.6023/cjoc201908015

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