Antiplasmodial and leishmanicidal activities of 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives.

Malaria and leishmaniasis are two of the World’s most important tropical parasitic diseases. Thirteen new 2-cyano-3-(4-phenylpiperazine-1-carboxamido) quinoxaline 1,4-dioxide derivatives (CPCQs) were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against erythrocytic forms of Plasmodium falciparum and axenic forms of Leishmania infantum. Their toxicity against VERO cells (normal monkey kidney cells) was also assessed. None of the tested compounds was efficient against Plasmodium, but two of them showed good activity against Leishmania. Toxicity on VERO was correlated with leishmanicidal properties

New salicylamide and sulfonamide derivatives of quinoxaline 1,4-di-N-oxide with antileishmanial and antimalarial activities

Continuing with the efforts to identify new active compounds against malaria and leishmaniasis, fourteen new 3-amino-1,4-di-N-oxide quinoxaline-2-carbonitrile derivatives were synthesized and evaluated for their in vitro antimalarial and antileishmanial activity against Plasmodium falciparum Colombian FCR-3 strain and Leishmania amazonensis strain MHOM/BR/76/LTB-012A. Further computational studies to analyze graphic SAR and ADME properties were undertaken. Results indicate that compounds with one halogenous group substituted in position 6 and 7 provide an efficient approach for further development of antimalarial and antileishmanial agents. In addition, interesting ADME properties were foun

New quinoxaline 1,4-di-N-oxide derivatives: Trypanosomaticidal activities and enzyme docking simulation

Two series of pyrazol and propenone quinoxaline derivatives were tested for parasiticidal activity (against amastigotes of Leishmania peruviana and trypomastigotes of Trypanosoma cruzi) and for toxicity against proliferative and non-proliferative cells. The pyrazol series was almost inactive against T. cruzi but, 2,6-Dimethyl-3-[5-(3,4,5-trimethoxy-phenyl)-4,5-dihydro-1H-pyrazol-3-yl] - quinoxaline 1,4-dioxide inhibited 50% of Leishmania growth at 8.9 µM with no impact against proliferative kidney cells and low toxicity against Thp-1 and murine macrophages. The compounds of the propenone series were moderately active against T. cruzi. Among them, 2 compounds were particularly interesting: (2E)-1-(7-Fluoro-3-methyl-quinoxalin-2-yl)-3-(3,4,5-trimethoxy-phenyl)-propenone, that showed a selective activity against proliferative cells (cancer and parasites), being inactive against normal murine peritoneal macrophages and (2E)-3-(3,4,5-Trimethoxy-phenyl)-1-(3,6,7-trimethyl-quinoxalin-2-yl)-propenone that was only active against Leishmania and inactive against the other tested cells. Furthermore in silico studies were performed for ADME properties and docking studies, both series of compounds respected the Lipinski’s rules and show linear correlation between tripanosomaticidal activities and LogP. Docking studies revealed that compounds of the second series could interact with the poly (ADP-ribose) polymerase protein of Trypanosoma cruzi

Analysis of additivity and synergism in the anti-plasmodial effect of purified compounds from plant extracts

In the search for antimalarials from ethnobotanical origin, plant extracts are chemically fractionated and biological tests guide the isolation of pure active compounds. To establish the responsibility of isolated active compound(s) to the whole antiplasmodial activity of a crude extract, the literature in this field was scanned and results were analysed quantitatively to find the contribution of the pure compound to the activity of the whole extract. It was found that, generally, the activity of isolated molecules could not account on their own for the activity of the crude extract. It is suggested that future research should take into account the “drugs beside the drug”, looking for those products (otherwise discarded along the fractionation process) able to boost the activity of isolated active compounds

Is crowd-funding appropriate to finance scientific research in the global South? Ethics in research for international development: environment, societies and health in the countries of Greater Mekong region

International audienc

Transmission of Traditional Medicinal Knowledge: a survey of two Hmong communities in Northern Laos.

International audienc