Development of a New Methodology for Dearomative Borylation of Coumarins and Chromenes and Its Applications to Synthesize Boron-Containing Retinoids.

Dearomative borylation of coumarins and chromenes via conjugate addition represents a relatively unexplored and challenging task. To address this issue, herein, we report a new and general copper (I) catalyzed dearomative borylation process to synthesize boron-containing oxacycles. In this report, the borylation of coumarins, chromones, and chromenes comprising functional groups, such as esters, nitriles, carbonyls, and amides, has been achieved. In addition, the method generates different classes of potential boron-based retinoids, including the ones with oxadiazole and anthocyanin motifs. The borylated oxacycles can serve as suitable intermediates to generate a library of compounds.

Base mediated synthesis of functionalized 2-(alkynyl)arylnitriles and their molecular docking study with aromatase receptor.

A simple, efficient, and transition metal-free approach to synthesize functionalized 2-(alkynyl)benzonitriles has been developed using suitably functionalized 2H-pyran-2-ones and 4-phenyl/trimethylsilanyl-but-3-yn-2-ones as precursors. The reaction proceeds in the presence of a base at room temperature to yield internal as well as terminal alkynes. The structure of the synthesized compound was confirmed by single-crystal X-ray analysis. The molecular docking study was performed to evaluate the binding mode of action of newly synthesized alkyne derivatives with known human breast cancer target receptor aromatase (PDB ID: 3EQM).

Base controlled diverse reactivity of allyl cyanide for synthesis of multi-substituted benzenes.

A base controlled regioselective 1,6-cyanoallylation of suitably functionalized 2H-pyran-2-ones has been demonstrated for the synthesis of various multi-substituted benzenes through a tandem process. We observed that lithium hydroxide provides a major product from α-attack and a minor product from γ-attack of allyl cyanide, while the use of sodium hydride as a base exclusively provides the product by γ-attack of allyl cyanide. We have also performed NMR experiments to understand the mechanistic pathway. The structure of the compound was confirmed by single crystal X-ray analysis.

Microwave assisted base dependent regioselective synthesis of partially reduced chromenes, isochromenes and phenanthrenes.

We have reported a microwave assisted base directed regioselective synthesis of partially reduced chromenes, isochromenes and phenanthrenes. Functionalized 4-(piperidin-1-yl)-5,6-dihydro-2H-benzo[h]-chromen-2-one-3-carbonitriles have been used as precursors, which on reaction with functionalized acetophenones in the presence of KOH in DMF under microwave irradiation yield (Z)-2-(2-aryl-5,6-dihydro-4H-benzo[f]isochromen-4-ylidene)acetonitriles. The use of NaH in DMF provides 3-aryl-1-(piperidin-1-yl)-9,10-dihydro phenanthrene-2-carbonitriles in excellent yield regioselectively. The use of cyclohexanone as a nucleophile source yields (Z)-2-(3,4,7,8-tetrahydro-1H-naphtho[2,1-c]chromen-6(2H)-ylidene)acetonitriles. The structure and geometry of isochromene have been proved without any ambiguity by single crystal X-ray diffraction.

Synthesis of 1-amino-2-aroyl/acetylnaphthalenes through a base mediated one pot inter and intramolecular C-C bond formation strategy.

A new precursor 2-(1-cyano-2,2-bis(methylthio)vinyl)benzonitrile has been synthesized by the reaction of 2-cyanomethylbenzonitrile, carbon disulfide and methyl iodide under basic conditions. The reaction of 2-(1-cyano-2,2-bis(methylthio)vinyl)benzonitrile with various functionalized aryl/heteroaryl methyl ketones or acetone under basic conditions afforded 4-amino-3-aroyl/heteroaroyl/acetyl-2-methylsulfanylnaphthalene-1-carbonitriles in good yields through a (5C + 1C) annulation strategy; this involves sequential intermolecular, followed by intramolecular, C-C bond formation reactions. The structure of the product was confirmed by single crystal X-ray crystallography.

A novel procedure for the synthesis of borylated quinolines and its application in the development of potential boron-based homeodomain interacting protein kinase 2 (HIPK2) inhibitors.

Herein, we demonstrate a Pd catalyzed C-4 borylation of structurally complex chloroquinolines with bis(pinacolato)diboron under relatively simple and efficient conditions. Moreover, the borylated quinolines were converted into oxaborole, trifluoroborate salt and boronic acid and also rendered in the Suzuki reaction successfully. The method was also applied for the synthesis of potential boron-based homeodomain interacting protein kinase 2 (HIPK2) inhibitors. The strategy opens up new avenues for the functionalization of quinolines as potential probes and pharmacological agents for future biomedical research.

The Recent Development of Tetrahydro-Quinoline/Isoquinoline Based Compounds as Anticancer Agents.

Tetrahydroquinoline and isoquinoline scaffolds are important class of heterocyclic compounds, which is implied for the development of new drugs and diagnostic for therapeutic function. Naturally occurring as well as synthetic tetrahydroquinolines/isoquinolines possess many different biological activities and have been testified as remarkable cytotoxic and potency in human cancer cell lines. Tetrahydroquinoline/isoquinoline based compounds displayed a key role in the development of anticancer drugs or lead molecules and acting through various mechanisms such as cell proliferation, apoptosis, DNA fragmentation, inhibition of tubulin polymerization, induced cell cycle arrest, interruption of cell migration, and modulation. The number of tetrahydroquinoline/isoquinoline derivatives has been reported as potent anticancer agents. Due to promising anticancer activities and wideranging properties of these molecules, we have compiled the literature for the synthesis and anticancer properties of various tetrahydroquinolines and isoquinolines. We have reported the synthesis of potent tetrahydroquinoline/isoquinoline molecules of the last 10 years with their anticancer properties in various cancer cell lines and stated their half-maximal inhibitory concentration (IC50). In addition, we also considered the discussion of molecular docking and structural activity relationship wherever provided to understand the possible mode of activity a target involved and structural feature responsible for the better activity, so the reader can directly find the detail for designing new anticancer agents.

Therapeutic Applications of Human and Bovine Colostrum in the Treatment of Gastrointestinal Diseases and Distinctive Cancer Types: The Current Evidence.

The incidence of gastrointestinal disorders (GID) and cancers is escalating all over the world. Limited consumption of colostrum by newborns not only weakens the immune system but also predisposes infants to microbial infections. Colostrum is nature's perfect food, sometimes referred to as the 'elixir of life'. Breast-fed infants have a lower incidence of GI tract infections than infants fed formula or cow's milk. As per WHO statistics, cancer is the most prevalent disease globally and causes 9.6 million deaths worldwide. The current strategies for treating cancer include chemotherapy, radiation, and surgery. However, chemotherapy and radiation exposure are usually associated with serious long-term side effects and deterioration in the quality of life (QOL) of patients. Furthermore, the hospitalization and medication costs for treating cancers are exorbitant and impose high economic burden on healthcare systems. People are desperately looking for cost-effective and affordable alternative therapies for treating GID and cancers. Therefore, there is an urgent need for clinically evaluating the anticancer compounds isolated from plants and animals. Such therapies would not only be economical and have fewer side effects, but also help to improve the QOL of cancer patients. Recently, bovine colostrum (BC) has caught the attention of many investigators to explore its anticancer potential in humans. BC impregnated dressings are highly effective in treating chronic wounds and diabetic foot ulcer. BC is rich in lactoferrin, a glycoprotein with strong antioxidant, anti-inflammatory, anti-cancer, and anti-microbial properties. Intravaginal application of BC tablets is effective in causing the regression of low-grade cervical intraepithelial neoplasia. The underlying mechanisms of BC at cellular, genetic, and molecular levels remain to be ascertained. Oral BC supplement is well-tolerated, but some people may experience problems such as flatulence and nausea. Well-designed, randomized, placebo-controlled, clinical trials are needed to access the therapeutic potential, long-term safety, and optimal doses of BC products. This review is aimed to highlight the anticancer potential of BC and its components, and the therapeutic applications of BC supplements in treating gastrointestinal diseases in children and adults. We also discuss the health promotion benefits and therapeutic potential of BC nutraceuticals in reducing the incidence of non-communicable diseases.

Redox-Responsive Dipeptide Nanostructures toward Targeted Cancer Therapy.

Materials that exhibit responsiveness toward biological signals are currently subjected to intense research in the field of drug delivery. In our study, we tried to develop cancer-targeted and redox-responsive nanoparticles (NPs) from disulfide-linked oxidized cysteine-phenylalanine (CFO). The NPs were conjugated with folic acid (FA) to specifically target cancer cells, and the presence of disulfide bonds would enabled the disintegration of the particles in the presence of elevated levels of glutathione (GSH) in cancer cells. Anticancer drug doxorubicin (Dox) was successfully loaded inside the disulfide-linked nanoparticles (CFO-Dox-NPs), which further demonstrated stimuli-responsive drug release in the presence of GSH. We have also demonstrated enhanced uptake of FA-derivatized NPs (FA-CFO-NPs) in cancerous cells (C6 glioma and B16F10 melanoma cells) than in normal cells (HEK293T cells) due to the overexpression of FA receptors on the surface of cancer cells. Cytotoxicity studies in C6 cells and B16F10 cells further revealed enhanced efficacy of Dox loaded (FA-CFO-Dox-NPs) as compared to the native drug. The findings of this study clearly demonstrated that the disulfide-linked nanoparticle system may provide a promising selective drug delivery platform in cancer cells.