%0 Journal Article
%T Aurones: A Promising Heterocyclic Scaffold for the Development of Potent Antileishmanial Agents
%A Marina Roussaki
%A Sofia Costa Lima
%A Anna-Maria Kypreou
%A Panagiotis Kefalas
%A Anabela Cordeiro da Silva
%A Anastasia Detsi
%J International Journal of Medicinal Chemistry
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/196921
%X A series of (Z)-2-benzylidenebenzofuran-3-(2H)-ones (aurones) bearing a variety of substituents on rings A and B were synthesized and evaluated for their antiparasitic activity against the intracellular amastigote form of Leishmania infantum and their cytotoxicity against human THP1-differentiated macrophages. In general, aurones bearing no substituents on ring A (compounds 4a¨C4f) exhibit higher toxicity than aurones with 4,6-dimethoxy substitution (compounds 4g¨C4l). Among the latter, two aurones possessing a 2¡ä-methoxy or a 2¡ä-methyl group (compounds 4i and 4j) exhibit potent antileishmanial activity ( £¿ M and £¿ M, resp.), comparable to the activity of the reference drug Amphotericin B, whereas they present significantly lower cytotoxicity than Amphotericin B as deduced by the higher selectivity index. 1. Introduction Leishmaniasis, an infectious disease caused by protozoan parasites belonging to the genus Leishmania (L.), is transmitted to humans through the bite of female phlebotomine sand flies infected with the parasite.This disease is manifested in three forms: cutaneous leishmaniasis (CL), which is the most common form, mucocutaneous leishmaniasis (MCL), and visceral leishmaniasis (VL) [1]. CL causes ulcers on the exposed parts of the human body which leave permanent scars when healed, whereas MCL causes the destruction of the mucous membranes of the nose, mouth, and throat cavities and surrounding tissues leading to serious disabling of the patient. Although they do not cause death of the patient, these two forms pose a serious social problem as a result of prejudice or even rejection of the disfigured patient from the community. VL is the most serious form of the disease which inevitably leads to death if left untreated [2]. Leishmaniasis is distributed in four continents and affects millions of people, especially in the poor developing countries where the lack of efficient medical care and resources, malnutrition, and weak immune system enhance the possibility of infection [3]. Moreover, co-infection with HIV is an emerging threat as the immunosuppressed HIV patients are especially vulnerable to VL infection. In fact, the majority of the VL cases reported in southern Europe involves HIV-infected patients [4]. In addition, in developed countries, where leishmaniasis is not endemic, the cases of infected population have increased over the last decade, in association with increasing international tourism, military operations, and the influx of immigrants from endemic countries [5]. Treatment of leishmaniasis lies exclusively on chemotherapy
%U http://www.hindawi.com/journals/ijmc/2012/196921/