大分子前药。十二。伯氨喹缀合物：合成与初步抗疟评价。

Macromolecular prodrugs. XII. Primaquine conjugates: synthesis and preliminary antimalarial evaluation.

作者信息

Rajić Zrinka, Kos Gabrijela, Zorc Branka, Singh Prati Pal, Singh Savita

机构信息

Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb Croatia.

出版信息

Acta Pharm. 2009 Mar;59(1):107-15. doi: 10.2478/v10007-009-0007-x.

DOI:10.2478/v10007-009-0007-x

PMID:19304563

Abstract

New primaquine conjugates 5-7 with glucosamine and two polymers of polyaspartamide type, poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA), were synthesized, characterized and screened for their antimalarial activity. The conjugates differed in the type of covalent bonding, length of the spacer between the polymeric carrier and drug, molecular mass and drug-loading. Blood-schizontocidal activity of the prepared conjugates was tested against Plasmodium berghei infection in Swiss mice. Polymeric conjugates showed better antimalarial activity than the glucosamine conjugate.

摘要

合成了新型伯氨喹与葡糖胺以及两种聚天冬酰胺类聚合物（聚[α,β-(N-2-羟乙基-DL-天冬酰胺)]（PHEA）和聚[α,β-(N-3-羟丙基-DL-天冬酰胺)]（PHPA））的缀合物5-7，对其进行了表征并筛选了抗疟活性。这些缀合物在共价键类型、聚合物载体与药物之间间隔物的长度、分子量和载药量方面存在差异。在瑞士小鼠中测试了所制备缀合物对伯氏疟原虫感染的血裂殖体杀灭活性。聚合物缀合物显示出比葡糖胺缀合物更好的抗疟活性。