112798-16-0Relevant articles and documents
Synthesis and in vitro evaluation of 4-trichloromethylpyrrolo[1,2-A] quinoxalines as new antiplasmodial agents
Primas, Nicolas,Suzanne, Peggy,Verhaeghe, Pierre,Hutter, Sébastien,Kieffer, Charline,Laget, Michèle,Cohen, Anita,Broggi, Julie,Lancelot, Jean-Charles,Lesnard, Aurélien,Dallemagne, Patrick,Rathelot, Pascal,Rault, Sylvain,Vanelle, Patrice,Azas, Nadine
, p. 26 - 35 (2014/07/07)
Thanks to a preliminary in vitro screening of several CCl 3-substituted-nitrogen containing heterocycles belonging to our chemical library, the 2-trichloromethylquinoxaline scaffold appeared to be of potential interest for developing new antiplasmodial agents. Then, combining these experimental results to the antimalarial properties reported for various pyrrolo[1,2-A]quinoxaline derivatives, an original series of fifteen 7-substituted-4-trichoromethylpyrrolo[1,2-A]quinoxalines was synthesized in a 4 to 5 reaction steps pathway. All molecules were evaluated in vitro toward both their antiplasmodial activity on the K1 multi-resistant Plasmodium falciparum strain and their cytotoxicity on the HepG2 human cell line. Thus, 3 hit molecules were identified, displaying IC50 values in the micromolar range and low cytotoxicity values, reaching good selectivity indexes, in comparison with the reference drugs chloroquine and doxycycline. Structure-activity relationship studies showed that the pyrrolo[1,2-A] quinoxaline scaffold can support selective antiplasmodial activity when substituted at position 4 by a CCl3 group. However, substitution at position 7 of the same scaffold is neither beneficial for cytotoxicity nor favourable for the solubility in the biological media.
