Search academic texts

Information × Registration Number 0216U006330, 0116U005357 , R & D reports Title 4-Thiazolidinone derivatives and related heterocyclic systems as prototypes of potential antitrypanosomal drugs popup.stage_title Head Lesyk Roman Bogdanovych, Доктор фармацевтичних наук Registration Date 16-12-2016 Organization Danylo Halytsky Lviv National Medical University popup.description2 A sub-libraries of new 4-tiazolidinone/thiazole derivatives bearing hydrazone fragment in position 2 of the basic heterocyclic core were designed based on the previous data of the structure - antitrypanosomal activity relationships. The synthetic methods for new compounds were working out and new derivatives of 4-azolidinones and related heterocycles based on [2+3] cyclocondensation were obtained. The structure and purity of the compounds were confirmed by physico-chemical data. Antitrypanosomal screening of synthesized compounds was performed and the directions of optimization of the structure of compounds of selected sub-libraries were determined. The new molecules bearing indanone or structurally related heterocyclic moiety were synthesized within hybride pharmacophore approach. The linked group between 4-tiazolidinone fragment and indanone-like core was the hydrazone fragment. The target compounds, namely N-[4-aryl-thiazole-2-yl]-N'-[2-(4-aryl)-1H-indole-3-ylmethylen]-hidrozines and 2-[(2-aryl-1H-indole-3-ylmethylen)-hidrazono]-3-(aryl)-tiazolidin-4-ones possesed the significant antitrypanosomal activity against Trypanosoma brucei gambiense and Trypanosoma brucei brucei in the micromolar concentration range. The toxicity of the compounds (200-400 mg/kg, acute toxicity, mice), allows to consider them as potential antitrypanosomal agents for further pharmacological study. Analysis of structure-activity relationships (SAR and QSAR) allowed to define direction for further chemical optimization of the identified hit-compounds. Product Description popup.authors Камінський Д.В. Крищишин А.П. Лесик Р.Б. Лозинський А.В. Нєктєгаєв І.О. popup.nrat_date 2020-04-02 Close