Primaquine-pyrimidine hybrids: synthesis and dual-stage antiplasmodial activity

Hardeep Kaur; Marta Machado; Carmen de Kock; Peter Smith; Kelly Chibale; Miguel Prudêncio; Kamaljit Singh

doi:10.1016/j.ejmech.2015.06.045

Primaquine-pyrimidine hybrids: synthesis and dual-stage antiplasmodial activity

Eur J Med Chem. 2015 Aug 28:101:266-73. doi: 10.1016/j.ejmech.2015.06.045. Epub 2015 Jun 29.

Authors

Hardeep Kaur¹, Marta Machado², Carmen de Kock³, Peter Smith³, Kelly Chibale⁴, Miguel Prudêncio², Kamaljit Singh⁵

Affiliations

¹ Department of Chemistry, UGC-Centre for Advanced Studies-II, Guru Nanak Dev University, Amritsar 143005, India.
² Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Av. Prof. Egas Moniz, 1649-028 Lisboa, Portugal.
³ Division of Pharmacology, Department of Medicine, University of Cape Town, Observatory 7925, South Africa.
⁴ Department of Chemistry, South African Medical Research Council Drug Discovery and Development Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 701, South Africa.
⁵ Department of Chemistry, UGC-Centre for Advanced Studies-II, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: [email protected].

PMID: 26142491
DOI: 10.1016/j.ejmech.2015.06.045

Abstract

A series of novel pyrimidine-primaquine hybrids were synthesized and their effectiveness against the blood and liver stages of malaria parasites was evaluated. The hybrids displayed enhanced liver stage in vitro activity against P. berghei liver stage infection.

Keywords: Antiplasmodial agents; Blood stage activity; Hybrid drugs; Liver stage activity; Primaquine; Pyrimidine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antimalarials / chemical synthesis*
Antimalarials / chemistry
Antimalarials / pharmacology*
Cell Line
Dose-Response Relationship, Drug
Humans
Liver / drug effects*
Liver / parasitology
Mice
Mice, Inbred C57BL
Molecular Structure
Parasitic Sensitivity Tests
Plasmodium berghei / drug effects*
Primaquine / chemistry
Primaquine / pharmacology*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Structure-Activity Relationship

Substances

Antimalarials
Pyrimidines
pyrimidine
Primaquine