Síntese e avaliação biológica de novos candidatos a fármacos antiparasitários contra Neospora caninum, um importante parasita no setor pecuário

Abstract

Parasites are responsible for several economic, social and public health problems worldwide, they are not limited to infection in humans, found as well in animals, representing a great problem in the veterinary sector. A parasite which defines these damages and shares many similarities with Toxoplasma gondii (responsible by abortions in humans), is Neospora caninum, considered the main cause of abortions in cattle, associated with cases of stillborn calves, and/or congenital malformation. Brazil is currently the largest holder of cattle for commercial purposes, the lack of treatments for this disease is a problem with greatest importance, the search for effective drugs for the treatment of this parasitosis is extremely relevant and urgent. In this sense, 70 compounds were planned using strategies in medicinal chemistry such as bioisosterism, with nitazoxanide (NTZ) being used as a model (lead) for isosteric exchanges, since it has proven activity against N. caninum, and molecular hybridization between NTZ and cinnamic acid, nucleus responsible for the inhibition of T. gondii formate and nitrite transport proteins. The products were obtained in considerable yields (16 to 99%) and many of them were easily purified by precipitation. All compounds were analyzed by spectroscopic (Infrared and Nuclear Magnetic Resonance) and spectrometric (High Resolution Mass Spectrometry) techniques. For biological evaluation, 40 compounds were submitted to the cytotoxicity test, since N. caninum is an obligatory intracellular parasite, making it essential to carry out the cell viability test before the anti-parasitic test (invasion), since the maintenance of the cell in the control against the parasite is of total relevance. Eleven compounds (4, 19, 22, 25, 28 e 60-64) showed low toxicity in host cells and were used in assays that evaluate the invasiveness of N. caninum, and two of them showed a promising profile with less than 50% invasiveness. Due to the lack of effective treatments against N. caninum, the present work represents a great contribution to the development of new neosporicidal agents.