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The emergence of diabetes mellitus (DM), one of the prevalent metabolic disorders, has increased at alarming rates around the globe in the past few decades. The early discovery of insulin paved the way for the broadened non-invasive anti-hyperglycemic drug therapies to manage and treat diabetes. Recently, insulin resistance in brain tissues has been considered a new hallmark of disease progression, leading to neurodegeneration. Tetrahydro γ-carbolines are privileged scaffolds with various activities against obesity, cancer, and central nervous system (CNS) diseases. The failure of Latrepirdine in clinical phase trials as anti-AD, prompted us to explore further the γ-Carboline derivatives with anti-diabetic activity. To address this, we have leveraged our expertise in drug design to develop tetrahydro γ-carboline derivatives and studied their effect on glucose uptake. All the compounds exhibited low cytotoxicity towards the mammalian cell line 3T3-L1. Next, we screened the 10 derivatives to identify the novel anti-diabetic activities using a fluorescent glucose analog 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)-2-deoxy-D-glucose) based on a glucose-uptake assay in differentiated 3T3-L1 adipocytes. Compound 11a has significantly increased glucose uptake at 100 µM compared to rH-Insulin. The dose optimization (1 nM-100 nM) of lead compounds for 2-NBDG-glucose uptake clearly indicated that 11a is superior compared to Insulin. The 11a is the close analog of Latrepirdine, an anti-histamine drug, reported for Alzheimer disease (AD). Further, to understand its anti-AD potential we carried out in silico docking studies with its probable targets, Acetylcholinesterase (AChE), 5-hydroxytryptamine (5HT6) receptor, Butyrylcholinesterase (BChE), and N-methyl-D-aspartate (NMDA) receptor. The docking studies revealed that 11a had stronger binding to these targets than Latrepirdine, correlating with the glucose uptake assay. Thus, 11a is a potential lead disease-modifying agent and could be considered for the management and treatment of type 2 DM and AD.

A new library of 1,2,3-triazole aryl-attached (4,6-dimethoxy-1,3,5-triazin-2-yl) thiazoles (11a–j) has been designed and synthesized and its structures were characterized by 1H NMR 13C NMR and mass spectral data. Further, these derivatives (11a-j) were evaluated for their anticancer activity against four human cancer cell lines, including PC3 (prostate cancer), A549 (lung cancer), MCF-7 (breast cancer) and A2780 (ovarian cancer) by employing the MTT method, and the obtained results were compared with etoposide. Among all the examined compounds, 11a, 11b, 11c, 11i and 11j displayed the most promising activity. Particularly, two compounds 11a and 11b possessed good activity.

A series of novel γ-Carboline derivatives were designed and synthesized using the Suzuki coupling reaction to identify the leads for the activity against cancer. Interestingly, these compounds were tested for their anticancer activity against the cell lines, particularly human cancer cell lines MCF7 (breast), A549 (lung), SiHa (cervix), and Colo-205 (colon). Most of the γ-Carboline derivatives showed potent inhibitory activity in four cancer cell lines, according to in vitro anticancer activity screening. Two compounds, specifically LP-14 and LP-15, showed superior activity in cancer cell lines among the γ-Carboline derivatives from LP-1 to LP-16. Additionally, the compound LP-14, LP-15 and Etoposide carried out molecular docking studies on human topoisomerase II beta in complex with DNA and Etoposide (PDB ID: 3QX3). The docking studies’ results showed that the derivative LP-15 was strongly bound with the receptor amino acid residues, including Glu477 and DC8 compared with the marked drug Etoposide.

This work describes a novel iron‐catalysed approach for the synthesis of aryl‐substituted benzimidazoles and benzoxazoles. The methodology employs reductive carbonylation using readily available aryl iodides and aryl amines as precursors, with carbon monoxide serving as the efficient carbonyl source. The reaction proceeds under mild conditions with the addition of hydrosilanes and bases. Notably, aryl aldehydes are generated in situ from the aryl iodides, which subsequently react with o‐phenylenediamine or 2‐aminophenol to afford the desired products in high yields. The structures of the synthesized benzimidazoles and benzoxazoles were confirmed using 1H and 13C NMR spectroscopy and mass spectrometry. [ABSTRACT FROM AUTHOR]

The total synthesis of the 16-membered Polyhydroxylated macrolide, Aspergillide D has been accomplished utilizing the Grignard reaction, Sharpless asymmetric epoxidation Regioselective ring opening of epoxy alcohol, Wittig olefination and Yamaguchi macrolactonisation as key steps. 3-butene-1-ol has been utilized as the starting material. [ABSTRACT FROM AUTHOR]

The facile N-arylation of imidazoles and amines with arylboronic acids were catalyzed by heterogeneous basic copper fluorapatite (CuFAP) in methanol at room temperature. The procedure was found to work well, with a variety of imidazoles and amines affording good to excellent yields of N-arylimidazoles and N-arylamines with reusability of the catalyst.

A new, simple, and efficient synthetic protocol has been developed for Carbonylative Sonogashira Coupling (CSC) with aryl iodides, aromatic terminal alkynes, and CO (2 atm) by using manganese chloride (MnCl2) as a catalyst. This method has shown a good‐to‐excellent yield of the desired products. Additionally, it was found to have ensured the synthesis of 2‐substituted flavones. [ABSTRACT FROM AUTHOR]

This article describes the synthesis of a new phosphine free tetradentate Pd catalyst using dl-2,3-diaminopropionic acid. The complex was characterized by Mass, IR, and 1H NMR. The catalyst is air stable at room temperature and non-hygroscopic. Application of this new catalyst to regioselective C–H activation on 1-substituted 1,2,3-triazole and indoles with aryl iodides to get corresponding C-5 and C-2 arylated products with satisfactory yields. All the products were characterized by spectroscopic studies. [ABSTRACT FROM AUTHOR]

This article presents information about the design and evolution of copper apatite catalysts for N-arylation of heterocycles with chloro- and fluoroarenes. N-Arylheterocycles are common motifs in pharmaceutical research. The N-arylation of heterocycles using chloro- and fluoroarenes is of importance, since this reaction involving C-Cl and C-F activation contributes to the fundamental understanding of the reactivity of such very stable bonds. In this direction, N-arylation of heterocycles with chloroarenes containing electron withdrawing groups by using copper oxide coated copper nanoparticles and electron donating groups by Pd catalysts in the presence of strong bases are performed.