Synthesis and Evaluation of c-Src Kinase Inhibitory Activity of Pyridin-2(1H)-one Derivatives

Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than 25 μM. Compound 1-[2-(dimethylamino)ethyl]-5-(2-hydroxy-4-methoxybenzoyl)pyridin-2(1H)-one (36) exhibited the highest c-Src kinase inhibition with an IC50 value of 12.5 μM. Further the kinase inhibitory potential of compound 36 was studied for EGFR, MAPK and PDK, however no significant activity was observed at the highest tested concentration (300 μM). These results provide insights for further optimization of this scaffold for designing the next generation of 2-pyridone derivatives as candidate Src kinase inhibitors

Synthesis of novel acrylyl pyranochromen-2-one derivatives and their antibacterial activity evaluation

482-496A series of fourteen pyranochromen-2-one acrylate derivatives has been synthesized by acid-catalyzed esterification reaction of the corresponding pyranochromen-2-one acrylic acids with various alcohols under reflux conditions. In order to have comparison of the activity profiles of esters and amides, the synthesis of ten pyranochromen-2-one acrylamides from corresponding acrylic acids using different coupling agents has also been carried out. All of the synthesized compounds have been fully characterized from their spectral data and evaluated for antibacterial activity against both Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). It is inferred form the results that the presence of hydroxyl group along with longer hydrophobic alkyl chain is favorable for a compound to inhibit bacterial growth, which can be used to design and develop the next generation of compounds with higher antibacterial efficacy

Polyglycerol-based hydrogels and nanogels: from synthesis to applications.

Hydrogels and nanogels have emerged as promising materials for biomedical applications owing to their large surface area and tunable mechanical and chemical properties. Their large surface area is well suited for bioconjugation, whilst the interior porous network can be utilized for the transport of valuable biomolecules. The use of biocompatible hydrophilic building blocks/linkers for the preparation of hydrogels and nanogels not only avoids undesired side effects within the biological system, but also retains high water content, thereby creating an environment which is very similar to extracellular matrix. Their tunable multivalency and hydrophilicity and excellent biocompatibility, together with ease of functionalization, makes polyglycerol macromonomers well suited for synthesizing cross-linked networks that can be used as extracellular matrix mimics. Here we provide an overview of the synthesis of polyglycerol-based hydrogels and nanogels for various biomedical applications

Synthesis and antibacterial activity screening of <em>N</em>- and <em>O</em>-substituted quinolin-2-one acetamide derivatives

1243-1250A series of new quinolin-2-one acetamide derivatives have been synthesized and characterized; their antibacterial potential investigated, against three Gram-positive pathogenic strains namely Bacillus cereus, Bacillus subtilis and Staphylococcus aureus and four Gram-negative pathogenic strains namely Pseudomonas aeruginosa, Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae by disc diffusion assay at a concentration of 250 μg/disc. Two of these compounds, which are O-substituted quinolin-2-one acetamides exhibit moderate activity against six bacterial strains B. cereus, B. subtilis, S. aureus, P. aeruginosa, E. coli and S. typhimurium

Fabrication of nanostructures through selfassembly of non-ionic amphiphiles for biomedical applications

Fabrication of self-assembled nanostructures with defined size and morphology represents a formidable challenge and thus, has gained tremendous momentum in research because of their potential applications in various biological systems. Herein, we report on the synthesis of novel non-ionic amphiphiles using 2,2-di(prop-2-yn-1-yl)propane-1,3-diol as a core further functionalized with poly(ethylene glycol) monomethyl ether and alkyl chains employing a chemo-enzymatic approach. Surface tension and fluorescence measurements along with dynamic light scattering studies revealed that all of the amphiphilic systems spontaneously self-assemble in aqueous solution, which is further supplemented by cryogenic transmission electron microscopy. The solubilization behavior of these systems as evidenced from UV-Vis and fluorescence spectroscopy and high performance liquid chromatography suggested the effective encapsulation of hydrophobic entities like Nile red, nimodipine, curcumin and dexamethasone. A comparative study with a standard excipient, Cremophor® ELP demonstrated that our nanocarriers exhibited superior/equivalent solubilization behavior for curcumin. Confocal laser scanning microscopy revealed efficient uptake of encapsulated dye in the cytosol of lung cancer cells, thus suggesting, that the reported amphiphilic systems can transport drugs into cells. A study of cytotoxicity showed that the synthesized amphiphilic systems are non-cytotoxic at the concentrations studied. The release profile of encapsulated Nile red incubated with/without a hydrolase enzyme Candida antarctica lipase demonstrated that the dye is stable in the amphiphilic nanostructures in the absence of enzyme for up to 12 days, however, more than 90% release of the dye occurred in 12 days when incubated with lipase. The results advocate the potential of these nanostructures as prospective drug delivery vehicles

Synthesis and characterization of novel benzoxazine-based arylidinyl succinimide derivatives

<p>1,4-Benzoxazine skeleton holds substantial promise for further exploration owing to its immense pharmacological potential. In this pursuit, a series of 20 novel benzoxazine-based arylidinyl succinimide derivatives (<b>23</b>–<b>42</b>) were synthesized in moderate to good yields by the reaction of ethyl 2-(7-(2,5-dioxo-2,5-dihydro-1<i>H</i>-pyrrol-1-yl)-3-oxo-2<i>H</i>-benzo[<i>b</i>][1,4]oxazin-4(3<i>H</i>)-yl)acetate (<b>22</b>) with various aromatic aldehydes under Wittig reaction conditions in the presence of triphenylphosphine and ethanol. All these synthesized compounds were fully characterized from their spectral data (¹H, ¹³C, and ²D NMR, IR, UV, high-resolution mass spectroscopy (HRMS)) and further confirmed by X-ray crystallographic analysis of a representative compound (<b>32</b>). Antibacterial activity of obtained arylidinyl succinimide derivatives was evaluated against both Gram-positive and Gram-negative bacterial strains and were found to exhibit insignificant activity as compared to the reference.</p

Non-ionic small amphiphile based nanostructures for biomedical applications.

Self-assembly of non-ionic amphiphilic architectures into nanostructures with defined size, shape and morphology has garnered substantial momentum in the recent years due to their extensive applications in biomedicine. The manifestation of a wide range of morphologies such as micelles, vesicles, fibers, tubes, and toroids is thought to be related to the structure of amphiphilic architectures, in particular, the choice of the hydrophilic and hydrophobic parts. In this review, we look at different types of non-ionic small amphiphilic architectures and the factors that influence their self-assembly into various nanostructures in aqueous medium. In particular, we focus on the explored structural parameters that guide the formation of various nanostructures, and the ways these structures can be used in applications ranging from drug delivery to cell imaging

Non-ionic small amphiphile based nanostructures for biomedical applications.

Self-assembly of non-ionic amphiphilic architectures into nanostructures with defined size, shape and morphology has garnered substantial momentum in the recent years due to their extensive applications in biomedicine. The manifestation of a wide range of morphologies such as micelles, vesicles, fibers, tubes, and toroids is thought to be related to the structure of amphiphilic architectures, in particular, the choice of the hydrophilic and hydrophobic parts. In this review, we look at different types of non-ionic small amphiphilic architectures and the factors that influence their self-assembly into various nanostructures in aqueous medium. In particular, we focus on the explored structural parameters that guide the formation of various nanostructures, and the ways these structures can be used in applications ranging from drug delivery to cell imaging