Theoretical Studies for the Discovery of Potential Sucrase-Isomaltase Inhibitors from Maize Silk Phytochemicals: An Approach to Treatment of Type 2 Diabetes.

A theoretical analysis of the potential inhibition of human sucrase-isomaltase (SI) by flavonoids was carried out with the aim of identifying potential candidates for an alternative treatment of type 2 diabetes. Two compounds from maize silks, maysin and luteolin, were selected to be studied with the structure-based density functional theory (DFT), molecular docking (MDock), and molecular dynamics (MD) approaches. The docking score and MD simulations suggested that the compounds maysin and luteolin presented higher binding affinities in N-terminal sucrase-isomaltase (NtSI) than in C-terminal sucrase-isomaltase (CtSI). The reactivity parameters, such as chemical hardness (η) and chemical potential (µ), of the ligands, as well as of the active site amino acids of the NtSI, were calculated by the meta-GGA M06 functional in combination with the 6-31G(d) basis set. The lower value of chemical hardness calculated for the maysin molecule indicated that this might interact more easily with the active site of NtSI, in comparison with the values of the acarbose and luteolin structures. Additionally, a possible oxidative process was proposed through the quantum chemical calculations of the electronic charge transfer values (∆N) between the active site amino acids of the NtSI and the ligands. In addition, maysin displayed a higher ability to generate more oxidative damage in the NtSI active site. Our results suggest that maysin and luteolin can be used to develop novel α-glucosidase inhibitors via NtSI inhibition.

In vitro and Quantitative and Structure Activity Relationship (QSAR) evaluation of the antifungal activity of terpenoid constituents of essential oils against Alternaria alternata and Fusarium oxysporum / Evaluación in vitro y QSAR (Quantitative and Structure-Activity Relationship) de la actividad antifúngica de terpenoides obtenidos de aceites esenciales frente a Alternaria alternata y Fusarium oxysporum

INTRODUCTION: Fungal genera Alternaria and Fusarium include human and plant pathogenic species. Several antifungals have been used for their control, but excessive use has contributed to resistance development in pathogens. An alternative to searching for and developing new antifungal agents is using essential oils and their main components, which have biological activities of interest in medicine and food production. OBJECTIVE: To evaluate in vitro and in silico the antifungal activities of terpenoids against Alternaria alternata and Fusarium oxysporum. MATERIALS AND METHODS: The minimum inhibitory concentration and minimum fungicidal concentration values of 27 constituents of essential oils used against Alternaria alternata and Fusarium oxysporum were evaluated in vitro. In addition, using genetic algorithms, quantitative models of the structure-activity relationship were used to identify the structural and physicochemical properties related to antifungal activity. RESULTS: The evaluated compounds proved to be effective antifungals. Thymol was the most active with a minimum inhibitory concentration of 91.6 ± 28.8 µg/ml for A. alternata and F. oxysporum. Quantitative structure-activity relationship models revealed the octanolwater cleavage ratio as the molecular property, and the phenols as the main functional group contributing to antifungal activity. CONCLUSION: Terpenoids exhibit relevant antifungal activities that should be incorporated into the study of medicinal chemistry. Inclusion of in silico assays in the in vitro evaluation is a valuable tool in the search for and rational design of terpene derivatives as new potential antifungal agents.

Introducción: Los géneros Alternaria y Fusarium contienen especies patógenas para los humanos y los cultivos. Para su control, se han utilizado diversos antifúngicos. Sin embargo, su uso desmedido ha contribuido al desarrollo de agentes patógenos resistentes. Una alternativa para buscar y desarrollar nuevos agentes antimicóticos son los aceites esenciales y sus componentes principales, los cuales poseen diversas actividades biológicas de interés para la medicina y en la preservación de alimentos. Objetivo: Evaluar in vitro e in silico las actividades antifúngicas de terpenoides contra Alternaria alternata y Fusarium oxysporum. Materiales y métodos: Se evaluaron in vitro las concentraciones inhibitorias mínimas y las concentraciones fungicidas mínimas de 27 constituyentes de aceites esenciales contra A. alternata y F. oxysporum. Además, mediante algoritmos genéticos, se crearon modelos cuantitativos de la relación estructura-actividad para determinar las propiedades estructurales y fisicoquímicas relacionadas con la actividad antifúngica. Resultados: Los compuestos evaluados mostraron ser antifúngicos activos. El timol fue el compuesto con mayor actividad, con un valor de concentración inhibitoria mínima de 91.6 ± 28.8 µg/ml, tanto para Alternaria alternata como para Fusarium oxysporum. Los modelos cuantitativos de la relación estructura-actividad incluyeron la avidez por los lípidos y los fenoles como los principales grupos funcionales que contribuyen en la actividad antifúngica. Conclusión: Los terpenoides poseen actividades antifúngicas relevantes para ser incorporados en el estudio de la química medicinal. La inclusión de pruebas in silico a la evaluación in vitro es una herramienta útil para la búsqueda y el diseño racional de derivados terpénicos como posibles agentes antifúngicos.

Terpenic Constituents of Essential Oils with Larvicidal Activity against Aedes Aegypti: A QSAR and Docking Molecular Study.

Aedes aegypti is a vector for the arbovirus responsible for yellow fever, Zika and Chikungunya virus. Essential oils and their constituents are known for their larvicidal properties and are strong candidates for mosquito control. This work aimed to develop a quantitative structure-activity study and molecular screening for the search and design of new larvicidal agents. Twenty-five monoterpenes with previously evaluated larvicidal activity were built and optimized using computational tools. QSAR models were constructed through genetic algorithms from the larvicidal activity and the calculation of theoretical descriptors for each molecule. Docking studies on acetylcholinesterase (AChE) and sterol carrier protein (SCP-2) were also carried out. Results demonstrate that the epoxide groups in the structure of terpenes hinder larvicidal activity, while lipophilicity plays an important role in enhancing biological activity. Larvicidal activity correlates with the interaction of the sterol-carrier protein. Of the 25 compounds evaluated, carvacrol showed the highest larvicidal activity with an LC50 of 8.8 µg/mL. The information included in this work contributes to describing the molecular, topological, and quantum mechanical properties related to the larvicidal activity of monoterpenes and their derivatives.

In vitro and Quantitative and Structure Activity Relationship (QSAR) evaluation of the antifungal activity of terpenoid constituents of essential oils against Alternaria alternata and Fusarium oxysporum / Evaluación in vitro y QSAR (Quantitative and Structure-Activity Relationship) de la actividad antifúngica de terpenoides obtenidos de aceites esenciales frente a Alternaria alternata y Fusarium oxysporum

Introducción. Los géneros Alternaria y Fusarium contienen especies patógenas para los humanos y los cultivos. Para su control, se han utilizado diversos antifúngicos. Sin embargo, su uso desmedido ha contribuido al desarrollo de agentes patógenos resistentes. Una alternativa para buscar y desarrollar nuevos agentes antimicóticos son los aceites esenciales y sus componentes principales, los cuales poseen diversas actividades biológicas de interés para la medicina y en la preservación de alimentos. Objetivo. Evaluar in vitro e in silico las actividades antifúngicas de terpenoides contra Alternaria alternata y Fusarium oxysporum. Materiales y métodos. Se evaluaron in vitro las concentraciones inhibitorias mínimas y las concentraciones fungicidas mínimas de 27 constituyentes de aceites esenciales contra A. alternata y F. oxysporum. Además, mediante algoritmos genéticos, se crearon modelos cuantitativos de la relación estructura-actividad para determinar las propiedades estructurales y fisicoquímicas relacionadas con la actividad antifúngica. Resultados. Los compuestos evaluados mostraron ser antifúngicos activos. El timol fue el compuesto con mayor actividad, con un valor de concentración inhibitoria mínima de 91.6 ± 28.8 pg/ml, tanto para Alternarla alternata como para Fusarium oxysporum. Los modelos cuantitativos de la relación estructura-actividad incluyeron la avidez por los lípidos y los fenoles como los principales grupos funcionales que contribuyen en la actividad antifúngica. Conclusión. Los terpenoides poseen actividades antifúngicas relevantes para ser incorporados en el estudio de la química medicinal. La inclusión de pruebas in silico a la evaluación in vitro es una herramienta útil para la búsqueda y el diseño racional de derivados terpénicos como posibles agentes antifúngicos.

Introduction. Fungal genera Alternaría and Fusarium include human and plant pathogenic species. Several antifungals have been used for their control, hut excessive use has contributed to resistance development in pathogens. An alternative to searching for and developing new antifungal agents is using essential oils and their main components, which have biological activities of interest in medicine and food production. Objective. To evaluate in vitro and in silico the antifungal activities of terpenoids against Alternaria alternata and Fusarium oxysporum. Materials and methods. The minimum inhibitory concentration and minimum fungicidal concentration values of 27 constituents of essential oils used against Alternaria alternata and Fusarium oxysporum were evaluated in vitro. In addition, using genetic algorithms, quantitative models of the structure-activity relationship were used to identify the structural and physicochemical properties related to antifungal activity. Results. The evaluated compounds proved to be effective antifungals. Thymol was the most active with a minimum inhibitory concentration of 91.6 ± 28.8 pg/ml for A. alternata and F. oxysporum. Quantitative structure-activity relationship models revealed the octanol-water cleavage ratio as the molecular property, and the phenols as the main functional group contributing to antifungal activity. Conclusion. Terpenoids exhibit relevant antifungal activities that should be incorporated into the study of medicinal chemistry. Inclusion of in silico assays in the in vitro evaluation is a valuable tool in the search for and rational design of terpene derivatives as new potential antifungal agents.

DFT calculation of the electronic properties of fluorene-1,3,4-thiadiazole oligomers.

Thiadiazole derivatives have been widely employed in the areas of pharmaceutical, agricultural, industrial, and polymer chemistry. The electronic and molecular structures of thiadiazoles are of interest because they have an equal number of valence electrons and similar molecular structures to thiophenes, which are currently used in the construction of organic solar cells due to their relatively high hole mobilities and good light-harvesting properties. For this reason, the electronic properties of fluorene-1,3,4-thiadiazole oligomers warrant investigation. In the present work, the structure of fluorene-1,3,4-thiadiazole with one thiadiazole unit in the structure was analyzed. This molecule was then expanded until there were 10 thiadiazole units in the structure. The band gap, HOMO and LUMO distributions, and absorption spectrum were analyzed for each molecule. All calculations were performed by applying the B3LYP/6-31G(d) chemical model in the Gaussian 03W and GaussView software packages. The electronic properties were observed to significantly enhance as the number of monomeric units increased, which also caused the gap energy to decrease from 3.51 eV in the oligomer with just one thiadiazole ring to 2.33 eV in the oligomer with 10 units. The HOMO and LUMO regions were well defined and separated for oligomers with at least 5 monomer units of thiadiazole.