Barbituric acid derivatives have been pharmacologically significant compounds for decades. The central nervous system effects are conditioned by the presence of the pyrimidine-trione ring and the nature of the substituent in position 5. Lipophilicity as one of the key molecular descriptors of biological activity for selected barbituric acid derivatives was determined experimentally, using reversed-phase thin layer chromatography (RP TLC18 F254s), in two solvent systems. The influence of the substituent’s nature and the effects of applied organic modifiers on the chromatographic behavior of the tested derivatives were examined. For the studied derivatives the values of the partition coefficient (logP) as a standard measure of lipophilicity and effective concentration (EC50) as a measure of acute toxicity for different test organisms were calculated applying the appropriate software packages. Dependence between the chromatographic parameters as assumed measures of lipophilicity and the software-derived biological activity parameters of the studied barbituric acid derivatives were studied by linear regression analysis.
In silico approach is increasingly used in modern design to establish the qualitative / quantitative dependence between structure, physico-chemical properties and biological activity of the new molecule. The selection and application of appropriate molecular descriptors are important step in this process. Given the presence of the amide group in numerous pharmacologically and biologically active molecules, in the pharmaceutical and chemical industries its formation represents an eternal challenge and a significant transformation in the design of the synthetic plan. Evaluation of the biological potential of selected amide derivatives included theoretical and experimental determination of their lipophilicity, analysis of their bioavailability, study of their pharmacokinetic predictors and ecotoxicity parameters. The parameters (RM0, m and C0) obtained by applying reversed-phase thin layer chromatography (RP TLC18 F254s) in the presence of two organic modifiers, as assumed measures of lipophilicity of the examined amide derivatives were correlated with the studied parameters of biological activity by the linear regression method. The quality of the obtained mathematical models was confirmed by the values of statistical validation parameters.
Derivatives of thiocarbohydrazone studied so far have shown great biological activity such as antioxidant, antimicrobial, and anticancer. Most of these compounds are bis-substituted derivatives, while monothiocarbohydrazones are much less investigated. Еighteen monothiocarbohydrazones were synthesized and subjected to physicochemical characterization in order to facilitate the examination of their potential biological activity and application in future studies. The structure of synthesized derivatives was confirmed with NMR and FT-IR spectroscopy, and with elemental analysis. For one of the compounds, single-crystal X-ray diffraction analysis was performed. Specific and non-specific molecular interactions were interpreted by LSER principles, using Catalan's model. For additional information about the dominance and influence of the interactions presented, correlations with Hansen's solubility parameters were calculated. Influence of the type and position of the substituent on absorption maxima was determined with LFER (linear free-energy relationship) principles, using Hammett's equation. Acidity constants of the synthesized compounds were theoretically calculated and experimentally determined. Moreover, the excitation of a molecule by a photon of UV-Vis light was interpreted by time-dependent density functional theory (TD-DFT) calculations of UV absorption bands, and intramolecular charge transfer (ICT) was quantified by calculations of the charge transfer distances (D CT ).
Many of carbohydrazone derivatives have shown a wide range of biological activities. In previous studies, these compounds have proven to be excellent anti-cancer, antitumor, antibacterial, antimicrobial and antioxidant agents. Monocarbohydrazones, as one of the carbohydrazone derivatives, have been slightly explored. Due to that reason, in this study, eight newly synthesized monocarbohydrazones were subjected to examinations by the use of three antioxidant tests. To determine the effectiveness of monocarbohydrazone as potential radical scavengers, DPPH (2,2-Diphenyl-1-picrylhydrazyl), ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (Ferric Reducing Antioxidant Power) assays were used. The obtained results could open the door for further studies of these compounds as biologically active substances.
Modern approach in the study of biologically active compounds includes the establishment of relationships between molecular structure, physicochemical properties and the behavior which studied compound can manifest in the biological medium. These examinantions are performed in the early stages of the design of future bioactive agent and require the knowledge of molecular descriptors that can point to its biological activity, including lipophilicity which occupies a key position. For the series of diphenylacetamide derivatives, lipophilicity is determined experimentally by thin-layer chromatography on reversed phase (RP TLC18 F254s), in mixtures of water and various organic modifiers and computationally, by using the relevant software packages. In order to estimate the potential acute toxicity of the tested diphenylacetamide derivatives, their effective concentrations, EC50, on the selected test organisms have been determined. Experimentally determined lipophilicity (RM 0 and m) is correlated with a standard measure of lipophilicity (log P), as well as with the selected parameters of toxicity. Thus it has been found that thin-layer chromatography on reversed phase can be used reliably for describing the lipophilicity and for the evaluation of the toxic effects of diphenylacetamide derivatives.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.