DESIGN AND DEVELOPMENT OF NEW CHEMICAL ENTITIES FOR THE TREATMENT OF PARASITIC ZOONOSES

MARTINEZ, S. R.; HERGERT, L. Y.; ACIAR, R. M. A.; RAVETTI, S.

Rosario, Santa Fé

Otro; II Reunión Internacional de las Ciencias Farmacéuticas; 2012

Universidad Nacional de Córdoba - Universidad Nacional de Rosario

Introduction Parasitic diseases remain a major public health problem, particularly in developing countries. The currently available pharmacotherapy for treating parasitosis is not effective and produces severe side effects. Furthermore, the prolonged and indiscriminate use has generated some resistance to drugs used, being a therapeutic inefficiency. Therefore, international organizations like the World Health Organization (WHO) has among its main objectives the design, synthesis and evaluation of new compounds with antiparasitic activity. Driven by this problem, we have proposed general objectives seeking new antiparasitic compounds that represent therapeutic alternatives, focusing on the optimization of pharmacokinetic and biopharmaceutical drug with proven clinical efficacy, as well as, evaluating new aspects related with the activity of these antimicrobial compounds in order to expand their potential therapeutic properties and study further mechanisms of action. Objectives Thymol (2-isopropil-5-metilfenol, TM), a p-cymene-derived compound, is widely used in medicine for its antimicrobial, antiseptic and disinfectant propierties. In this study thymol´s structure was chemically modified by derivatization of the free hydroxyl group of TM with two different amines (piperazine and piperidine) by a carbamate linkaje. Materials and Methods The novel derivatives were obtained by conjugating the tymol´s hydroxyl group with piperidine and piperazine, using N, N-carbonyldiimidazole (CDI) in anhydrous conditions. Groups transporters have been selected based on the needs that have been identified in current treatments of zoonoses (low availability, development of resistance, adverse effects, etc.). Results The new derivatives were prepared following the methods of the conventional organic synthesis with high yields. The techniques for identification, purification and purity control were: thin layer chromatography, recrystallization, infrared spectroscopy and nuclear magnetic resonance. The pharmacological activity, toxicity and resistance of the new chemical entities (NCEs) obtained to different etiological agents of zoonoses will be evaluated. Conclusion Because derivatives of p-cymene have leishmanicidal activity and basic structures are considered important for development of novel antiparasitic drugs, we suggest that thymol and its derivatives could be potential candidates in the treatment of parasitic diseases.