Design, Synthesis of 3-(Aryl)-1-(2-p-tolylthiazol-4-yl)prop-2-en-1-ones as Alpha(α)-Amylase Inhibitors.

α-Amylase inhibition is vital in controlling diabetic complications. Herein, we have synthesized a hybrid scaffold based on thiazole-chalcone to access α-amylase inhbition. The proposed structures were verified with spectroscopic techniques (UV-Vis., FT-IR, 1H-, 13C-NMR, and elemental analysis). The synthesized compounds were evaluated for their α-amylase and antioxidant potential. In vitro hemolytic assay was performed to test biocompatibility of all compounds. Among tested compounds, 4 c (IC50=3.8 µM), 4 g (IC50=14.5 µM), and 4 f (IC50=17.1 µM) were found excellent α-amylase inhibitors. However, none of the tested compounds exhibited significant antioxidant activity. All compounds showed less lysis than Triton X-100, but compounds 4 f and 4 h had the least lysis at all tested concentrations and were found to be safe for human erythrocytes. Molecular docking study was performed to evaluate the binding interactions of ligands with human pancreatic α-amylase (HPA). The binding score -8.09 to -8.507 kcal/mol revealed strong binding interactions in the ligand-protein complex. The docking results supplemented the observed α-amylase inhibition and hence augment the scaffold to serve as leads for the antidiabetic drug development.

Synthesis of Thiazole-Chalcone Hybrid Molecules: Antioxidant, Alpha(α)-Amylase Inhibition and Docking Studies.

The molecular hybrid approach is very significant to combat various drug-resistant disorders. A simple, convenient, and cost-effective synthesis of thiazole-based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1-(2-phenylthiazol-4-yl)ethanone (3) was used as the main intermediate for the synthesis of 3-(arylidene)-1-(2-phenylthiazol-4-yl)prop-2-en-1-ones (4a-f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achieved via different spectroscopic techniques (UV, FT-IR, 1 H- and 13 C-NMR) and elemental analysis. All synthesized compounds were tested for their α-amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested with in vitro haemolytic assay. All tested compounds showed moderate to excellent α-amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic α-amylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated the in vitro amylase inhibition results, i.e., 3-(3-Methoxyphenyl)-1-(2-phenylthiazol-4-yl)prop-2-en-1-one (4e) exhibited lowest IC50 value 54.09±0.11  µM with a binding energy of -7.898 kcal/mol.

Antioxidant and Hepatoprotective Activities of Acacia jacquemontii Stem Extract against High-fat and CCl4-induced Liver Injury in Rat's Model.

BACKGROUND: Chronic liver injury leads to liver inflammation and fibrosis, activating myofibroblasts in the liver and secreting extracellular matrix proteins that make the fibrous scar. OBJECTIVES: The purpose of our study was to characterize the polyphenolic content present in Acacia jacquemontii stem and evaluate its antioxidant and hepatoprotective activity. METHODS: The phenolic contents in Acacia jacquemontii polyphenolic extract (AJPPE) were characterized using high-performance liquid chromatography (HPLC). The hepatoprotective and antioxidant activity of AJPPE were determined through biochemical parameters (ALT, AST, and ALP), lipid profile (TC, TG, HDL, and LDL), antioxidant biomarkers (SOD, LPO, GSH, and CAT), anti-fibrotic activity (collagen deposition), and histopathological analysis. RESULTS: HPLC analysis of AJPPE showed the presence of polyphenols, including chlorogenic acid, P-coumaric acid, caffeic acid, and kaempferol, in a remarkable therapeutic range. Results of the in vivo analysis showed a significant decrease in the level of lipid profile, including LDL (low-density lipoprotein), TC (total cholesterol), triglycerides, liver function markers (AST, ALT, and ALP), collagen deposition and significantly increased the level of anti-oxidative biomarkers (CAT, SOD, LPO, and GSH) by using AJPPE. CONCLUSION: The above-mentioned results have shown that AJPPE possesses significant antioxidative and hepatoprotective effects. Furthermore, histopathological results also supported the antioxidant and hepatoprotective potential of AJPPE.

ZnO nanoparticles produced in the culture supernatant of Bacillus thuringiensis ser. israelensis affect the demographic parameters of Musca domestica using the age-stage, two-sex life table.

BACKGROUND: Indiscriminate use of broad-spectrum insecticides can have deleterious effects on insects and the environment. The use of nanoparticles synthesized from microbes has recently gained importance as a safe alternative to conventional insecticides. Recently, zinc oxide (ZnO) nanoparticles synthesized using Bacillus thuringiensis have shown insecticidal potential; however, in addition to its acute toxicity, it is necessary to determine possible sublethal effects at the organismal level to understand the toxicity of a new insecticide. Bt-derived enzymes such as nitrate reductase and other biomolecules play a vital role in the reduction of metal ions to metal nanoparticles. Here, we assessed the acute toxicity and sublethal effects of ZnO nanoparticles produced in the culture supernatant of B. thuringiensis ser. israelensis (Bti) as a reducing agent on the biological traits of Musca domestica. RESULTS: Concentration-response larval bioassays using different concentrations of ZnO-Bti-supernatant nanoparticles revealed LC10 , LC20 , LC50 and LC90 values of 4.17, 6.11, 12.73 and 38.90 µg g-1 of larval diet, respectively. Exposure of M. domestica larvae to two concentrations (LC10 and LC20 ) resulted in a lengthened developmental time (egg to adult) and preoviposition period, and reduced fecundity, survival, longevity and oviposition period. Furthermore, population parameters including net reproductive rate, mean generation time, age-specific survival rate, fecundity, life expectancy and reproductive values, analyzed following age-stage and two-sex life table theory, were significantly decreased after exposure to these concentrations of ZnO-Bti-supernatant nanoparticles compared with the control. CONCLUSION: ZnO-Bti-supernatant nanoparticles were shown to be toxic to M. domestica. Exposure of M. domestica to low concentrations of ZnO-Bti-supernatant nanoparticles resulted in negative transgenerational effects on progeny production in this fly. © 2022 Society of Chemical Industry.

Defining Wider Indications for Stoppa Repair Other Than Recurrent Hernias.

Managing complex inguinal hernias has been a constant challenge for surgeons and its treatment is not without challenges with the routine current techniques. Complex inguinal hernias especially recurrent have been managed by the Rives-Stoppa technique which is an established suture-less, tension-free, and absolute method of treatment with minimal recurrence rates. Traditionally, this surgical technique is most indicated in recurrent inguinal hernias, but we aim to assess the usefulness of this procedure for the treatment of complex inguinal hernias in individuals presenting for the first time. We report four varied cases of complex inguinal hernias, repaired by the open Rives-Stoppa technique, and discuss its indications, technique of repair, and current status.