A Qsar Study on Thiourea Derivatives - New Approaches in Drug Development

Abstract

The ongoing resistance to antibiotics constraints the research activity to design and develop new molecules, intended to overcome these necessities. In the current study, a series of organic compounds have been investigated for their properties, correlated to the potential of crossing biological membranes, consequently targeting a specific protein that would trigger an infectious disease in the body. On the matter, quantitative structureactivity relationship (QSAR) properties and molecular docking studies have been carried out for seven thiourea derivatives. The highly promising compounds have been nominated by software that ascertain if a specific molecule has an intended behaviour in the internal medium of the organism. RezumatRezistența continuă la antibiotice constrânge activitatea de cercetare spre dezvoltarea și proiectarea de noi molecule, menite să depășească aceste necesități. În studiul actual au fost investigate proprietățile unei serii de compuși organici, aceste proprietăți fiind corelate cu potențialul de traversare prin membranele biologice și, în final, cu țintirea unei proteine responsabile de instalarea infecției. În acest sens, proprietățile QSAR și studiile de andocare moleculară au fost efectuate pentru șapte derivați ai tioureei. Cei mai promițători compuși au fost selectați prin intermediul unor programe software, capabile să determine dacă o anumită moleculă are un comportament specific în mediul intern al organismului.

New N-acyl Thiourea Derivatives: Synthesis, Standardized Quantification Method and In Vitro Evaluation of Potential Biological Activities

“…The present study aimed to continue the hypothesis traced in the previous research paper [34], regarding the antimicrobial activity of a series of thiourea derivatives with heterocyclic nuclei (thiazole, benzothiazole, pyridine and pyrimidine). The evaluated compounds, 1a-1g, are referred to in the cited source as A.01-A.07.…”

“…Considering the literature cited in the present paper [2,6,[29][30][31] and sustained by the conclusions traced after completing the molecular docking studies [34,45], the next step was the development of a synthesis strategy based on the advantage of merging two pharmacophores of thiourea and a heterocyclic ring (thiazole, benzothiazole, pyridine and pyrimidine) in a single molecular entity.…”

“…Considering the global threat of antimicrobial resistance and the lack of novel antiinfective drugs, developing novel antimicrobial agents remains one of the main goals in medicinal chemistry. Given these considerations and to continue our efforts to develop novel antimicrobial agents as bioactive lead candidates, we designed [34] and synthesized thiourea derivatives carrying a heterocyclic nucleus (1a-1g).…”

“…The benzo [d]thiazole-based N-acyl thiourea derivatives (1a-1g) were designed and synthesized according to a previously published method, with punctual modifications [34,35], characterized by in silico and experimental approaches and evaluated for their biological properties. Furthermore, a routine quality control method for quantitative evaluation of the most promising compound (1d) has been developed and validated by reversed-phase high-performance liquid chromatography (RP-HPLC).…”

In Silico Screening and in Vivo Evaluation of Potential Analgesic Effect of New Neurotensin (Nt8-13) Peptide Mimetics

“…It can also be used to predict their absorption, distribution, metabolism and excretion. Some literature sources provided different logP values as follows: a compound would pass brain barrier at logP value of approximately 2, oral and intestinal absorption are reached for 1.35 -1.8 values, and sublingual absorption requires logP values higher than 5 [25]. The miLogP values found for all synthesised peptides are in the ranges of -3.31 to -4.33 (Table I), which is an indicator of their hydrophilic nature.…”