Síntesis de Pirazoles e Isoxazoles Obtenidos de Derivados Curcuminoides y Predicción del Metabolismo empleando herramientas computacionales

Abstract

In recent scientific advances, various alternatives have been found for the production of complexes that exhibit biological activity (antifungal and antibacterial). Due to the complexity of finding a 100% effective solution, methodologies have been proposed to demonstrate effectiveness in treating bacteria, fungi, and other biological factors. As an alternative to the aforementioned, we have proposed research and methodologies for the synthesis of curcuminoid complexes, to subsequently conduct in silico tests using various computational software and determine their possible effectiveness for the development of future biological tests employing this type of compounds. It has been demonstrated thru various studies that curcuminoid complexes incorporating O-N (isoxazole) and N-H (pyrazole) groups exhibit high antibacterial and antifungal activity. With this research work, the aim is to initiate the study of the pharmacokinetics of these new molecules using various software and simulators that can predict the characteristics of lipophilicity and/or solubility in water, as well as their metabolism and permeation in relevant physiological membranes such as the blood-brain barrier, hepatic, endocrine, pulmonary, among others. Understanding this information thru the analysis of in silico studies will facilitate the identification of certain relevant functional groups in the molecules under study, to take them into account in future research and prevent the formation of potential highly toxic reactive metabolites. In the following work, the synthesis process for obtaining curcumin derivatives is shown, followed by the formation of their corresponding isoxazole and pyrazole complexes, their physical and chemical characterization, and based on in silico studies, determine how these compounds are metabolized in the body in case they are administered orally. The aim is to understand these new molecules; their pharmacokinetic behavior and identify the ADME (Absorption, Distribution, Metabolism, Excretion) processes they would undergo if used as drugs, and determine their possible adverse and/or toxic effects using predictive software. Similarly, in order to measure the toxicity of the compounds to be synthesized, toxicological tests will be conducted using lettuce seeds (Lactuca sativa).