In Silico Exploration of Isoxazole Derivatives of Usnic Acid: Novel Therapeutic Prospects Against α-Amylase for Diabetes Treatment.

Diabetes mellitus (DM) a metabolic disorder characterized by high blood sugar levels causing damage to various organs over time. Current anti-diabetic drugs have limitations and side effects, prompting a search for new inhibitors targeting the α-amylase enzyme. This study aims to discover such inhibitors from thirty isoxazole derivatives of usnic acid using in silico approaches. The potential inhibitory effects of compounds were investigated using ADMET, molecular docking, molecular dynamic simulation, principal component analysis and density functional theory studies. ADMET analysis exhibited a wide range of physicochemical, pharmacokinetic, and drug-like qualities with no significant side effects which were then investigated using molecular docking experiment to determine the lead compound with the best binding affinity for the α-amylase enzyme. All compounds showed good binding affinity against α-amylase enzyme (-7.9 to -9.2 kcal/mol) where compound-13 showed the best binding affinity of -9.2 kcal/mol forming hydrogen bonds with Leu162, Tyr62, Glu233 and Asp300 amino acids. Furthermore, the binding posture and the stability of the compound-13-α-amylase enzyme complex was confirmed by molecular dynamic simulation experiment. Moreover, compound-13 showed binding energy value of -27.92 ± 5.61 kcal/mol, which indicated it could be an α-amylase inhibitor. Additionally, the reactivity of compound-13 was further confirmed by density functional theory analysis. The above findings suggest compound-13 to be a potential α-amylase inhibitor in DM. And setting the stage for further in vitro and in vivo experimental validation.

Selected phytochemicals of Momordica charantia L. as potential anti-DENV-2 through the docking, DFT and molecular dynamic simulation.

Dengue fever is now one of the major global health concerns particularly for tropical and sub-tropical countries. However, there has been no FDA approved medication to treat dengue fever. Researchers are looking into DENV NS5 RdRp protease as a potential therapeutic target for discovering effective anti-dengue agents. The aim of this study to discover dengue virus inhibitor from a set of five compounds from Momordica charantia L. using a series of in-silico approaches. The compounds were docked into the active area of the DENV-2 NS5 RdRp protease to obtain the hit compounds. The successful compounds underwent additional testing for a study on drug-likeness similarity. Our study obtained Momordicoside-I as a lead compound which was further exposed to the Cytochrome P450 (CYP450) toxicity analysis to determine the toxicity based on docking scores and drug-likeness studies. Moreover, DFT studies were carried out to calculate the thermodynamic, molecular orbital and electrostatic potential properties for the lead compound. Moreover, the lead compound was next subjected to molecular dynamic simulation for 200 ns in order to confirm the stability of the docked complex and the binding posture discovered during docking experiment. Overall, the lead compound has demonstrated good medication like qualities, non-toxicity, and significant binding affinity towards the DENV-2 RdRp enzyme.Communicated by Ramaswamy H. Sarma.

Elucidating the alkene hydrogenation reaction based on cotton textile reduced graphene oxide under the influence of external electric field: Illustration of new noble method.

The hydrogenation reaction of alkene is one of the most used industrial chemical process for various materials of daily life and energy consumption. This is a heterogeneous reaction and traditionally carried out by metallic catalysis. However, these conventional catalytic hydrogenations of alkene suffer from various setbacks such as catalyst poisoning, less recyclability and are environmentally unfriendly. Therefore, in recent years, researchers have been trying to develop the alternatives to metal catalysis hydrogenation of alkene. Heterogeneous catalysis under the external electric field is considered the future of green catalysis. In this paper, we report a comprehensive investigation dealing with the theoretical basis for simulating the phenomenon of heterogeneous catalysis, on a molecular level, under an external electric field. The illustration of the prospect as well as the effects of the mostly used catalytic systems, reduced graphene oxide, under the influence of external electric fields is provided. Moreover, a noble method of alkene hydrogenation reaction based on cotton textile reduced graphene oxide (CT-RGO) under the influence of an external electric field is introduced. The corresponding theoretical investigation was carried out within the framework of the density functional theory (DFT) method using first-principles calculations. The study has been carried out by elucidating DFT calculations for three different proposed catalytic systems, namely without electricity, with electricity and with an external electric field of 2 milli-Atomic unit. The obtained results indicate that adsorption energy of H2 on the CT-RGO surface is significantly higher when the electric field is applied along the bond axis, suggesting thereby that hydrogenation of alkene can be induced with CT-RGO catalyst support under external electric fields. The obtained results shed light on the effect of the external electricity field on the graphene-hydrogen complex, the activation energy of graphene radicals to achieve the transition states as well as the adsorption of the hydrogen atoms over the graphene surface. Altogether, the theoretical results presented herein suggested that the proposed catalytic system holds promise for facilitating the alkene hydrogenation under external electric fields.

Highly sensitive pork meat detection using copper(ii) tetraaza complex by electrochemical biosensor.

Three copper(ii) tetraaza complexes [Cu(ii)LBr]Br (1a), [Cu(ii)L(CIO4)](CIO4) (2a) and [Cu(ii)L](CIO4)2 (2b), where L = 5,5,7,12,12,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-7,14-diene were prepared and confirmed by FTIR, 1HNMR and 13CNMR. The binding interaction of complex (1a, 2a, 2b) with calf thymus DNA (CT-DNA) was investigated using UV-vis absorption, luminescence titrations, viscosity measurements and molecular docking. The findings suggested that complex 1a, 2a and 2b bind to DNA by electrostatic interaction, and the strengths of the interaction were arranged according to 2b > 1a > 2a. The differences in binding strengths were certainly caused by the complexes' dissimilar charges and counter anions. Complex 2b, with the biggest binding strength towards the DNA, was further applied in developing the porcine sensor. The developed sensor exhibits a broad linear dynamic range, low detection limit, good selectivity, and reproducibility. Analysis of real samples showed that the biosensor had excellent selectivity towards the pork meat compared to chicken and beef meat.

Crystal structure and Hirshfeld analysis of 2-[bis-(1-methyl-1H-indol-3-yl)meth-yl]benzoic acid.

In the title compound, C26H22N2O2, the dihedral angles between the 1-methyl-indole units (A and B) and the benzoic acid moiety (C) are A/B = 64.87 (7), A/C = 80.92 (8) and B/C = 75.05 (8)°. An intra-molecular C-H⋯O inter-action arising from the methyne group helps to establish the conformation. In the crystal, R 2 2(8) carb-oxy-lic acid inversion dimers linked by pairs of O-H⋯O hydrogen bonds are observed. A Hirshfeld surface analysis shows that the greatest contributions are from H⋯H, C⋯H/H⋯C and O⋯H/H⋯O contacts (percentage values = 54.6%, 29.6% and 10.1%, respectively).

2,4-Di-chloro-N-[eth-yl(2-hy-droxy-eth-yl)carbamo-thio-yl]benzamide.

In the title compound, C12H14Cl2N2O2S, the mol-ecule adopts a cis conformation with respect to the di-chloro-benzoyl group against the thiono group about the C-N bond. However, the di-chloro-benzene group and the thio-urea moiety are twisted by 75.41 (8)°. An intra-molecular N-H⋯O hydrogen bond occurs between the amido H atom and hydroxyl O atom. In the crystal, O-H⋯S and O-H⋯O hydrogen bonds link the molecules, forming chains along the b-axis direction.

(Z)-4-Chloro-N-(1-{2-[3-(4-chloro-benzoyl)ureido]eth-yl}imidazolidin-2-yl-idene)benzamide.

The title compound, C(20)H(19)Cl(2)N(5)O(2)S, was obtained from the reaction of 4-chloro-benzoyl isothio-cyanate with diethyl-ene-triamine. The imidazolidine ring is slightly twisted with an N-C-C-N torsion angle of 15.4 (4)°, while the thio-urea moiety maintains its trans-cis geometry. The mol-ecule is stabilized by intramolecular N-H⋯O hydrogen bonds. The crystal structure features N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds and π-π interactions between benzene rings with a centroid-centroid distance of 3.607 (3) Å.