Citation: 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 shu

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 ^a ,
Liu Zhijun ^a,b ,
Li Yanbing ^a ,
He Yepu ^a ,
Lin Xiaohong ^b ,
Chen Heru ^a,c,,

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

Corresponding author: Chen Heru, thrchen@jnu.edu.cn
Received Date: 10 August 2019
Revised Date: 21 September 2019
Available Online: 9 February 2019
Fund Project: Project supported by the Natural Science Foundation of Guangdong Province (No. 2018B030311020)the Natural Science Foundation of Guangdong Province 2018B030311020

Figures(2)

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 (P_e) 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.
- drug synthesis,
- procarbazine,
- drug design,
- targeted anti-cancer,
- fibroblast activation protein-α
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