Assessment of the dual role of Lyonia ovalifolia (Wall.) Drude in inhibiting AGEs and enhancing GLUT4 translocation through LC-ESI-QTOF-MS/MS determination and in silico studies

Introduction: Diabetes mellitus (DM) is a metabolic disorder that results in glucose accumulation in the blood, accompanied by the production of advanced glycation end products (AGEs) through glycation of cellular proteins. These AGEs interfere with insulin signaling and prevent GLUT4 membrane translocation, thereby promoting the accumulation of more glucose in the blood and causing post-diabetic complications.Methods: In this study, we examine the anti-diabetic potential of Lyonia ovalifolia (Wall.) Drude, a well-known ethnomedicinal plant of the Indian Himalayas. Considering its various medicinal properties, we analyzed its ethanolic extract and various solvent fractions for in vitro antiglycation activity and antidiabetic potential, i.e., stimulation of GLUT4 translocation.Result and Discussions: The results showed that the extract and fractions exhibited increased antiglycation activity and an increased level of GLUT4 translocation. Analysis of a further 12 bioactive compounds of ethanolic extract, identified through LC-ESI-QTOF-MS/MS, revealed the presence of three new compounds: leucothol B, rhodoterpenoids A, and leucothol A. Moreover, we performed molecular docking of identified compounds against key proteins of diabetes mellitus: the sirtuin family of NAD (+)-dependent protein deacetylases 6 (SIRT6), aldose reductase (AR), and tyrosine kinase (TK). The results showed that flavonoid luteolin showed the best binding affinity ((−12.3 kcal/mol), followed by eriodictyol, astilbin, and syringaresinol. An ADMET study showed that luteolin, eriodictyol, astilbin, and syringaresinol may be promising drug candidates belonging to the flavonoid class of compounds, with no harmful effects and complying with all the drug-likeness guidelines. Furthermore, molecular dynamics (MD) simulations on a 50 ns timescale revealed that AR protein was most stable with luteolin throughout the simulation period. Therefore, this study reveals for the first time that L. ovalifolia plays an important role in insulin homeostasis, as shown in in vitro and in silico studies

Silver(I)-Catalyzed Regioselective Construction of Highly Substituted α‑Naphthols and Its Application toward Expeditious Synthesis of Lignan Natural Products

A novel route has been developed for regioselective synthesis of highly substituted α-naphthols, binaphthols, and anthracenol through silver­(I) catalyzed C­(sp³)–H/C­(sp)–H, C­(sp²)–H/C­(sp)–H functionalization of β-ketoesters and alkynes, respectively, in a single step using water as a solvent. This protocol exhibited broad substrate scope and paved the way for synthesis of anticancer arylnaphthalene lignan natural products such as diphyllin, taiwanin E, and justicidin A with excellent selectivity

Copper(II) Catalyzed Expeditious Synthesis of Furoquinoxalines through a One-Pot Three-Component Coupling Strategy

Microwave assisted one-pot transformation has been developed for the synthesis of biologically significant polysubstituted furoquinoxalines in good to excellent yields through a copper­(II) catalyzed three-component coupling of <i>o-</i>phenylene­diamine, ethyl­glyoxalate, and terminal alkyne, known as A³-coupling, followed by 5<i>-endo-dig</i> cyclization

Molecular Iodine Promoted Divergent Synthesis of Benzimidazoles, Benzothiazoles, and 2‑Benzyl-3-phenyl-3,4-dihydro‑2<i>H</i>‑benzo[<i>e</i>][1,2,4]thiadiazines

An unprecedented formation of a new class of 2-benzyl-3-phenyl-3,4-dihydro-2<i>H</i>-benzo­[<i>e</i>]­[1,2,4]­thiadiazines has been discovered during the course of benzimidazole and benzothiazole synthesis, through the molecular iodine-mediated oxidative cyclization with a new C–N and S–N bond formation at ambient temperature

Synthesis, Structure–Activity Relationships, and Biological Studies of Chromenochalcones as Potential Antileishmanial Agents

Antileishmanial activities of a library of synthetic chalcone analogues have been examined. Among them, five compounds (<b>11</b>, <b>14</b>, <b>16</b>, <b>17</b>, <b>22</b>, and <b>24</b>) exhibited better activity than the marketed drug miltefosine in in vitro studies against the intracellular amastigotes form of Leishmania donovani. Three promising compounds, <b>16</b>, <b>17</b>, and <b>22</b>, were tested in a L. donovani/hamster model. Oral administration of chalcone <b>16</b>, at a concentration of 100 mg/kg of body weight per day for 5 consecutive days, resulted in >84% parasite inhibition at day 7 post-treatment and it retained the activity until day 28. The molecular and immunological studies revealed that compound <b>16</b> has a dual nature to act as a direct parasite killing agent and as a host immunostimulant. Pharmacokinetics and serum albumin binding studies also suggest that compound <b>16</b> has the potential to be a candidate for the treatment of the nonhealing form of leishmaniasis