Síntesis, caracterización y evaluación in vitro frente a epimastigotes de Trypanosoma cruzi de un nuevo derivado del timol.

CLEMENTE CAMILA M; INDA AYELEN; RAVETTI SOLEDAD; ALLEMANDI DANIEL A; ROBLEDO SARA; HERGERT LISANDRO Y

Mar del Plata

Otro; Reunión Anual de sociedades de biociencia. SAIC. SAFE. SAB. SAP. AACYTAL. NANOMED-ar.; 2019

Sociedad Argentina de Farmacología Experimental

SYNTHESIS, CHARACTERIZATION AND IN VITRO EVALUATION AGAINST TRYPANOSOMA CRUZI EPIMASTIGOTES OF A NEW THYMOL DERIVATIVE.Unidad Temática: Química MedicinalAbstract/Resumen: INTRODUCTION. Neglected Infectious Diseases (NIDs) are a group of infectious diseases, many of them parasitic, which mainly afflict the poorest people and with limited access to health services. NIDs have received limited attention despite their magnitude and impact on global public health. Chagas disease is a NID and is the major health problem in Latin America, affecting nearly 6 million people. The current treatment for this disease has numerous disadvantages: low therapeutic index, high cost, prolonged therapeutic schemes, side effects (such as skin rashes, nausea, gastrointestinal disorders), teratogenicity and drug resistance. This is why the search for new drugs that are more effective and better tolerated by patients is essential. OBJECTIVE. Synthesis, characterization and in vitro biological evaluation of a new chemical entity derived from the monoterpenic compound thymol against Trypanosoma cruzi. STUDY DESIGN. The derivative was obtained from the conjugation of the free hydroxyl group of thymol with the aliphatic alcohol n-pentanol. The synthesis of the derivative was carried out in two consecutive stages, the first involves the reaction of thymol with N,N-carbonyldiimidazol under nitrogen atmosphere in dichloromethane and the second, the reaction of the intermediary formed with the n-pentanol alcohol. Once the reaction is finished, successive extractions are made in distilled water. The reaction was monitored by thin layer chromatography (TLC) with a mobile phase Hexane: Ethyl Acetate, 6:4. The evaluation of cytotoxicity was carried out by means of the MTT colorimetric test on line U-937 (ATCC CRL-1593.2) with four serial dilutions of the derivative (50-12.5-3.125-0.78 µg/mL). The evaluation of the antitripanosomic activity in vitro was made by the colorimetric method with human macrophages U-937 infected with epimastigotes of T. cruzi strain of Tulahuen. The derivative was added in a series of concentrations (50-12.5-3.125-0.78 µg/mL). RESULTS. The synthesis was simple, economical and with good yields. Thymol and the new derivative were unequivocally identified by nuclear magnetic resonance spectroscopy (1H-RMN, 13C-RMN, COSY, HSQC and HMBC) and infrared and both showed moderate activity against T. cruzi. The new derivative showed lower cytotoxity than the starting compound. CONCLUSION. The structural modification allowed to improve its efficiency on the model used, presenting a higher selectivity index than the starting compound thymol.