Contribution in the Malaria Control of Substituted 5-chloro-3,4-dihydro-1H-pyrano[3,4-b]-1,10-phenanthrolinone Compounds: Antiplasmodial and Cytotoxic Activities

Cheikh Sall; Insa Seck; Samba Fama Ndoye; Matar Seck; Alexis Valentin; Yves Blache

Cheikh Sall Laboratoire de Chimie, UFR des Sciences de la Sant�, Universit� de Thi�s, BP 967 Thi�s, S�n�gal.
Insa Seck Laboratoire de Chimie Organique et Th�rapeutique, Facult� de M�decine de Pharmacie et d�Odontologie, Universit� Cheikh Anta Diop de Dakar, BP 5005 Dakar-Fann, S�n�gal.
Samba Fama Ndoye Laboratoire de Chimie Organique et Th�rapeutique, Facult� de M�decine de Pharmacie et d�Odontologie, Universit� Cheikh Anta Diop de Dakar, BP 5005 Dakar-Fann, S�n�gal.
Matar Seck Laboratoire de Chimie Organique et Th�rapeutique, Facult� de M�decine de Pharmacie et d�Odontologie, Universit� Cheikh Anta Diop de Dakar, BP 5005 Dakar-Fann, S�n�gal.
Alexis Valentin Universit� de Toulouse, Pharma-DEV, IRD, Universit� Paul Sabatier, 31062 Toulouse Cedex 4, France.
Yves Blache Universit� de Toulon, MAPIEM, EA 4323, 83957 La Garde, France.

Keywords: Malaria disease, Plasmodium falciparum, 1,10-phenanthrolinone, antimalarial activity

Abstract

Background: Malaria is one of the most common parasitic disease in tropical and subtropical regions. Plasmodium falciparum, one of the causative agent of malaria is resistant to many type of antimalarial drugs. This study present in vitro assessment of the antiplasmodial activity of substituted phanthrolinone compounds.

Methods: A series of 7 substituents were used to substitute the chlorine on the 5 position in the 5-chloro-3,4-dihydro-1H-pyrano[3,4-b]-1,10-phenanthrolinone ring. In vitro antiplasmodial activities were evaluated on chloroquine-sensitive and resistant strains of P. falciparum.

Results: The results showed that compounds 7 and 8 possessing N,N-diethylamino side chain had the best antiplasmodial activities. In addition, the cytotoxic activities were evaluated on HeLa cells and compound 8 was the least cytotoxic of all studied compounds.

Conclusion: The synthesis and antimalarial activity of substituents of compound 2 were carried out. This study has shown that compounds with basic and lipophilic substituents exhibited the best antiplasmodial activity. Drug resistance of parasites and anopheles remains a major problem in the malaria burden. At present, the best chemically solution to eradicate definitely this disease is establishment of new antimalarial drug which is exempt of any resistance. The 1,10-phenanthroline skeleton was synthesized and studied for it potential new antimalarial activity. Its pharmacomodulation led to several compounds among which compound 8 showed higher activity as compared to the parent compound 2. This compound should be used for future pharmacomodulation particularly to open the lactone ring in basic medium.