Design and Development of Novel 2-(Morpholinyl)-N-substituted Phenylquinazolin-4-amines as Selective COX-II Inhibitor.

BACKGROUND: A novel series of 2-(Morpholin-4-yl)-N-phenylquinazolin-4- amine derivatives were synthesized and confirmed with spectral and elemental techniques. METHODS: The compounds were tested for analgesic and anti-inflammatory activity by various pain models in rodents whereas the selectivity towards COX-2 receptor is determined by in vitro assay. RESULTS: Screening results of compounds exhibited comparable biological activity with that of standard compound Indomethacin used for study. Compound 5d was found to be significantly potent with respect to its anti-inflammatory and analgesic activity with substantial COX-II selectivity. CONCLUSION: In silico analysis by molecular docking and 3D-QSAR studies justifies activity profile of compound 5d, suggesting that it may have potential for further evaluation and development as lead molecule for therapy in pain management.

Bone Health and Natural Products- An Insight.

Bone metabolism involves a complex balance between matrix deposition, mineralization, and resorption. Numerous evidences have revealed that dietary components and phytoconstituents can influence these processes, through inhibition of bone resorption, thus exhibiting beneficial effects on the skeleton. Various traditional herbal formulae in ayurvedic and Chinese medicine have shown demonstrable benefits in pharmacological models of osteoporosis. The present review discusses normal bone metabolism and disorders caused by bone disruption, with particular reference to osteoporosis and current therapeutic treatment. Furthermore the effects of constituents from natural products on bone tissue are explained, with relevant evidences of efficacy in various experimental models.

Mycobacterial siderophore: A review on chemistry and biology of siderophore and its potential as a target for tuberculosis.

Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis is known to secrete low molecular mass compounds called siderophores especially under low iron conditions to chelate iron from host environment. Iron is essential for growth and other essential processes to sustain life of the bacterium in the host. Hence targeting siderophore is considered to be an alternative approach to prevent further virulence of bacterium into the host. This review article presents classification of siderophores, their role in transporting iron into the tubercular cell, biosynthesis of mycobactins, viability of siderophore as a therapeutic target and also focuses on overview on various approaches to target siderophore. The approaches encompass mutation effect on genes involved in siderophore recycling, synthetic as well as natural compounds that can inhibit further spread of bacterium by targeting siderophore.

Dendrimers: A versatile nanocarrier for drug delivery and targeting.

Dendrimers are novel polymeric nanoarchitectures characterized by hyper-branched 3D-structure having multiple functional groups on the surface that increases their functionality and make them versatile and biocompatible. Their unique properties like nanoscale uniform size, high degree of branching, polyvalency, water solubility, available internal cavities and convenient synthesis approaches make them promising agent for biological and drug delivery applications. Dendrimers have received an enormous attention from researchers among various nanomaterials. Dendrimers can be used as a carrier for diverse therapeutic agents. They can be used for reducing drug toxicities and enhancement of their efficacies. The present review provide a comprehensive outline of synthesis of dendrimers, interaction of dendrimer with guest molecules, properties, characterization and their potential applications in pharmaceutical and biomedical field.

DNA gyrase inhibitors: Progress and synthesis of potent compounds as antibacterial agents.

DNA gyrase is classified as topoisomerase II, an ATP-dependent enzyme that is vital in the transcription, replication of DNA and chromosome segregation processes. It plays a crucial role in all bacteria except higher eukaryotes and this makes it a desirable and viable therapeutic target for development of new antibacterial agents. Fluoroquinolones are commonly used effective antibacterial agents that target DNA gyrase, however the spectrum of side-effects and emerging bacterial resistance with no new drugs in the antibacterial pipeline has fuelled intensive research in this area. New chemical entities with varied scaffolds possessing DNA gyrase inhibiting properties have been determined by screening chemical libraries that could serve as good leads for antibacterial drug development. A wide range of natural products and protein-based compounds have been identified and studied as DNA gyrase inhibitors and this adds a huge amount of structural diversity that can be exploited and harnessed in the discovery of new antibacterial agents. The development of new chemical compounds with DNA gyrase inhibitory activity (from natural sources, random screens or rational design) will further validate/corroborate the potential of this enzyme as a useful target. This review presents an overview of the DNA gyrase inhibitors obtained from natural and synthetic sources, their syntheses schemes and spectrum of biological activity of a variety of scaffolds and their analogues. The authors hope to provide focused direction for development of new chemical entities, synthetic routes for analogue synthesis, structure activity relationships and biological activity. The most potent ones can be used as templates to design novel compounds targeting DNA gyrase and are effective against resistant bacterial strains and biofilms.

Cyclodextrin-based nanosponges: A critical review.

Cyclodextrin-based nanosponges (CD-NS) are innovative cross-linked cyclodextrin polymers nanostructured within three-dimensional network. CD-NS are highly porous nanoparticles characterized by crystalline or amorphous structure, spherical shape and swelling properties. Different cross-linkers provide variety of nanosponges. The polarity, dimension of the polymer mesh and release of entrapped molecule can be easily tuned by varying the type of cross-linker and degree of cross-linking. The site-specific targeting can be achieved by conjugating various ligands on the surface of nanosponge. They offer unique advantage of controlled release and are biologically safe and biodegradable material. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances and as innovative carrier in pharmaceuticals, cosmetics, protein/peptide delivery, diagnostics, enzyme-catalysed reactions, environmental control and agrochemistry.

Inclusion Complexation of Etodolac with Hydroxypropyl-beta-cyclodextrin and Auxiliary Agents: Formulation Characterization and Molecular Modeling Studies.

The present investigation was aimed to prepare inclusion complexes of a therapeutically important nonsteroidal anti-inflammatory drug, etodolac (ETD) with hydroxypropyl-beta-cyclodextrin (HP-ß-CD) and to study the effect of l-arginine (l-Arg) as an auxiliary agent on the complexation efficiency of HP-ß-CD to improve aqueous solubility and the dissolution property of ETD. The binary and ternary complexes were prepared by physical mixing, coevaporation, and spray drying methods. The complexes were characterized using differential scanning colorimetry (DSC), Fourier transform-infrared spectroscopy (FT-IR), and powder X-ray diffraction (PXRD) studies. The mechanism of inclusion interaction of guest and host was established through 1H NMR, molecular docking, and molecular dynamics studies. On the basis of preliminary screening studies, l-Arg was found to be the most efficient auxiliary agent for the present research problem. The change in crystallinity of ETD was evident from DSC and PXRD studies which indicated the formation of new solid forms. A remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HP-ß-CD was observed in the presence of l-Arg in ternary complexes with improvement in solubility and dissolution of ETD than binary complexes. However, inclusion complexes of ETD obtained by computational studies is in good correlation with the results obtained through experimental methods. More stable complex formation with l-Arg was confirmed by molecular simulation studies too. Thus, the present study led to the conclusion that the ternary complex of ETD-HP-ß-CD-l-Arg could be an innovative approach to augment the solubility and dissolution behavior of ETD.