Synthesis, antidiabetic activity and molecular docking study of rhodanine-substitued spirooxindole pyrrolidine derivatives as novel α-amylase inhibitors.

In a sustained search for novel α-amylase inhibitors for the treatment of type 2 diabetes mellitus (T2DM), we report herein the synthesis of a series of nineteen novel rhodanine-fused spiro[pyrrolidine-2,3'-oxindoles]. They were obtained by one-pot three component [3 + 2] cycloaddition of stabilized azomethine ylides, generated in situ by condensation of glycine methyl ester and the cyclic ketones 1H-indole-2,3-dione (isatin), with (Z)-5-arylidine-2-thioxothiazolidin-4-ones. The highlight of this protocol is the efficient high-yield construction of structurally diverse rhodanine-fused spiro[pyrrolidine-2,3'-oxindoles] scaffolds, including four contiguous stereocenters, along with excellent regio- and diastereoselectivities. The stereochemistry of all compounds was confirmed by NMR and corroborated by an X-ray diffraction study performed on one derivative. All cycloadducts were evaluated in vitro for their α-amylase inhibitory activity and showed good α-amylase inhibition with IC50 values ranging between 1.49 ± 0.10 and 3.06 ± 0.17 µM, with respect to the control drug acarbose (IC50 = 1.56 µM). Structural activity relationships (SARs) were also established for all synthesized compounds and the binding interactions of the most active spiropyrrolidine derivatives were modelledby means of molecular insilico docking studies. The most potent compounds 5 g, 5 k, 5 s and 5 l were further screened in vivo for their hypoglycemic activity in alloxan-induced diabetic rats, showing a reduction of the blood glucose level. Therefore, these spiropyrrolidine derivatives may be considered as promising candidates for the development of new classes of antidiabetic drugs.

Prevalence and molecular detection of Staphylococcus aureus resistance to antibiotics.

In Algeria, the issue of antibiotic resistance is on the rise, being the Staphylococcus aureus infection as a significant concern of hospital-acquired infections. The emergence of antibiotic resistance in this bacterium poses a worldwide challenge. The aim of this study aims to establish the incidence of S aureus strains in Algeria as well as identify phenotypic and genotypic resistance based on the "mecA" and "nuc" genes. From 2014 to 2017, a total of 185 S aureus strains were isolated from patients at a hospital in the city of Rouïba, Algiers the number of isolates was slightly higher in males at 58.06% compared to females at 41.94%, resulting in a sex ratio of 1.38. the Oxacillin and Cefoxitin DD test (1 µg oxacillin disk and 30 µg cefoxitin disk) identified 42 strains as resistant. The results indicated high resistance to lactam antibiotics, with penicillin having a 100% resistance rate. There was also significant resistance to oxacillin (51.25%) and cefoxitin (50%). This resistance was frequently associated with resistance to other antibiotic classes, such as aminoglycosides (50%) and Macrolides (28.29%). To confirm methicillin-resistant characteristics, a polymerase chain reaction (PCR) multiplex was conducted on 10 isolates (6 SARM; 4 MSSA) on a phenotypic level. Three isolates tested positive for "mecA," while 7 were negative. All strains carry the nuc gene, which is specific to S aureus. In Algeria, the incidence of S aureus resistance is slightly lower compared to other countries, but it is increasing over time. It is now more crucial than ever to restrict the proliferation of multidrug-resistant strains and reduce undue antibiotic prescriptions. To achieve this, it is vital to keep updated on the epidemiology of this bacterium and its antibiotic susceptibility. This will enable the formulation of appropriate preventive control measures to manage its progression.

Thymus algeriensis and Thymus fontanesii: Chemical Composition, In Vivo Antiinflammatory, Pain Killing and Antipyretic Activities: A Comprehensive Comparison.

This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, mainly rosmarinic acid and its derivatives, dominated the T. algeriensis extract, while the phenolic diterpene carnosol and the methylated flavonoid salvigenin, prevailed in T. fontanesii extract. Molecular docking study was carried out to estimate the anti-inflammatory potential and the binding affinities of some individual secondary metabolites from both extracts to the main enzymes involved in the inflammation pathway. In vitro enzyme inhibitory assays and in vivo assays were used to investigate the antioxidant and anti-inflammatory activities of the extracts. Results revealed that both studied Thymus species exhibited antioxidant, anti-inflammatory, analgesic, and antipyretic effects. They showed to be a more potent antioxidant than ascorbic acid and more selective against cyclooxygenase (COX-2) than diclofenac and indomethacin. Relatively, the T. fontanesii extract was more potent as COX-2 inhibitor than T. algeriensis. In conclusion, Thymus algeriensis and Thymus fontanesii may be interesting candidates for the treatment of inflammation and oxidative stress-related disorders.

Study of hypocholesterolemic activity of Algerian Pistacia lentiscus leaves extracts in vivo

Abstract Plants are a large source of new bioactive molecules with therapeutic potentials. However, only a small amount of worldwide plants have been phytochemically investigated. The aqueous and ethanolic extracts of Pistacia lentiscus L., Anacardiaceae, leaves were evaluated for hypocholesterolemic activity in vivo. In this study, hypercholesterolemia was induced in animals by feeding them high cholesterol (1%) food. The extracts of P. lentiscus were orally administered at a dose of 200 mg/kg body weight along with a high cholesterol diet for thirty successive days. Lipid parameters such as total cholesterol, triacylglyceride, low density lipoprotein, very low density lipoprotein and high density lipoprotein were measured in the plasma. Total phenol and flavonoid contents were also evaluated. Flavonoid content was found to be more present in the ethanolic extract (8.218 ± 0.009 mg of QE/g) compared to the aqueous extract (3.107 ± 0.014 mg of QE/g). The administration of P. lentiscus extracts produced a significant decrease in total cholesterol, triacylglyceride and low density lipoprotein-cholesterol (154.6 ± 18.10, 71.2 ± 4.38 and 99.36 ± 18.77 mg/dl respectively) in the ethanolic extract, while the aqueous extract showed a significant decrease in total cholesterol and triacylglyceride (203.6 ± 9.18 and 97.6 ± 3.57 mg/dl respectively). The results of the investigation demonstrated that P. lentiscus leaf extract has hypocholesterolemic properties and might be used for the prevention of hypercholesterolemia associated disorders.