Bioactive constituents from Tinospora cordifolia (willd.): Isolation, synthesis and their immunomodulatory activity.

Traditional medicinal plants have been used for centuries for their immunomodulatory properties and therapeutic potentials. The present study aims to investigate the immunomodulatory constituents from traditional medicinal plant, Tinospora cordifolia (willd.).

Immunomodulatory Plant Natural Products as Therapeutics against Inflammatory Skin Diseases.

Frequently occurring inflammatory skin conditions such as psoriasis, dermatitis, acne, including skin cancer, wounds and other disorders arising out of premature skin aging, deteriorate skin health and adversely impact human life. Even though several synthetic compounds have evolved for treating these skin conditions, natural-product-based therapeutics are gaining popularity with growing evidence of their efficacy and safety for treating skin disorders. Many of these inflammatory skin diseases have underlying disturbances in our immune system and immunomodulatory natural products provide solutions for their effective treatment and aid in understanding the underlying mechanism of such inflammatory skin conditions.

Design, synthesis and biological evaluation of novel lipophilic 2, 5-disubstituted tetrazole analogues of muramyl dipeptide as NOD2 agonists.

A focused library of six new 2, 5-disubstituted tetrazole (2, 5-DST) analogues of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) as potential immunomodulators were synthesized by the bioisosteric replacement of α-amide of d-isoglutamine with 5-substituted tetrazole (5-ST). Another parameter 'lipophilicity' was also considered to improve the pharmacological properties of MDP through the alkylation of 5-substituted tetrazole during synthesis. In total, six 2, 5-DST analogues of MDP were synthesized and bio-evaluated for the study of human NOD2 stimulation activity in the innate immune response.

Synthesis and immunopharmacological evaluation of novel TLR7 agonistic triazole tethered imidazoquinolines.

Toll-like receptors-7 and -8 are expressed abundantly on antigen-presenting cells, and their agonists make potential adjuvant candidates for the development of new efficacious vaccines. In view of the importance of new efficacious imidazoquinoline based adjuvants, herein we have synthesized a focused library of a new class of imidazoquinolines retaining the -isobutyl substitution of an imidazole moiety as in imiquimod and introduced a 1,2,3-triazolyl moiety upon alkyl substitution at the imidazolemethyne carbon employing triazolyl click chemistry. All the novel analogues were characterized using various spectroscopic techniques and the target specificity of these molecules was determined using HEK TLR7/8 transfected cell lines.

Synthesis and Immunological Activity of Novel Oligo(ethylene glycol) Analogues of α-Galactosylceramide.

CD1d-arbitrated activation of i-NKT cells by α-galactosylceramide results in the effective secretion of Th1 and Th2 cytokines, with adjuvanticity skewed toward Th2 immunity. However, the polarization of immune response could be achieved by suitable modification of the glycolipid structure. In the current study, novel glycolipids with an amphiphilic oligo ethylene glycol lipid moiety bearing the benzyloxy group at the terminus on the acyl arm of sphingosine, exhibited CD1d ligand binding as quantified by IL-2 cytokine production.

Synthesis and biological evaluation of novel 2-azido muramyl dipeptide as NOD2 agonistic adjuvants.

Novel 2-Azido muramyl dipeptide was synthesized by the bio-isosteric replacement of the N-acetyl group of the muramic acid fragment with the azide functionality at the C2 position. In order to examine the effect of hydrophilic-lipophilic balance on the adjuvant activity, derivatives were synthesized by removing protecting groups sequentially to tune the polarity. Amongst five novel azido derivatives of MDP studied here, di- and mono-benzylated azido derivatives 10 and 11 exhibited good DENV specific antibody(IgG) response with Th1 polarization compared to parent compound Muramyl dipeptide (MDP) whereas all five new derivatives responded positively to NOD2 agonistic assays with compound 10 showing highest stimulation.

Novel 1,2,3-triazole-tethered PamCAG conjugates as potential TLR-2 agonistic vaccine adjuvants.

A focused library of water soluble 1,2,3-triazole tethered glycopeptide conjugates derived from variety of azido-monosaccharides and aliphatic azido-alcohols were synthesized through manipulation at the C-terminus of PamCAG and screened for their potential as TLR2 agonistic adjuvants against HBsAg antigen. In vitro ligand induced TLR2 signal activation was observed with all the analogues upon treatment with HEK blue TLR2 cell lines. Conjugate derived from ribose (6e), which exhibited pronounced HBsAg specific antibody (IgG) titer also shown enhanced CD8+ population indicating superior cell mediated immunity compared to standard adjuvant PamCSK.

Characterization and photoprotective potentiality of lime dwelling Pseudomonas mediated melanin as sunscreen agent against UV-B radiations.

Prolonged exposure to Ultra Violet Radiation (UVR) adversely alters the functions of many skin cell types causing skin cancer and photoaging, which had led to increase in demand for more safe and natural sunscreens against UVR. The present study focuses on production, structural characterization and evaluation of photoprotective nature of melanin pigment derived from lime dwelling Pseudomonas sp. Melanin was characterized by solubility, UV-Vis, FT-IR, C-CPMAS, ESI-MS spectroscopy, including particle size, melting point and elemental analyses.

Cationic pH-Responsive Polycaprolactone Nanoparticles as Intranasal Antigen Delivery System for Potent Humoral and Cellular Immunity against Recombinant Tetravalent Dengue Antigen.

Research on amalgamation of an antigen with a delivery system for developing a potent mucosal vaccine that elicits both cellular and humoral response has captured immense attention these days. Cationic delivery systems being the first choice for mucosal antigen delivery, despite being effective, are associated with inherent problems like cytotoxicity. Therefore, the quest for developing a precise system that can effectively deliver antigen to immune cells without adverse toxic effect has led to the use of partial cationic systems which are mostly humoral immune mediators.

Comprehensive Analysis of Secondary Metabolites in (Lichenized Ascomycetes, Parmeliaceae) Using UPLC-ESI-QTOF-MS/MS and Pro-Apoptotic Activity of Barbatic Acid.

Considering the importance of ultra-performance liquid chromatography-electrospray ionization-quadrupole time of flight-tandem mass spectrometry (UPLC-ESI-QTOF-MS/MS) hyphenated techniques for analysis of secondary metabolites from crude extracts, the present study was aimed at identification of secondary metabolites in acetone extract of the lichen . From our study, 19 compounds were tentatively identified through comparison of exact molecular masses from their MS/MS spectra, mass fragmentation studies and comparison with literature data. In addition, potent cytotoxic activity of extract prompted us to isolate four compounds, 18-hydroxy-dihydroalloprotolichesterinic acid (), neuropogolic acid (), barbatic acid () and usnic acid () from this extract which were adequately identified through mass spectrometry and NMR spectroscopy.

Squalane-based emulsion vaccine delivery system: composition with murabutide activate Th1 response.

Emulsions play an important role in present-day subunit vaccine delivery. Squalane-based emulsion was formulated using surfactants viz., Pluronic F68, Span 85 along with Murabutide (MB) as immunepotentiator.

Chitosan stabilized nasal emulsion delivery system for effective humoral and cellular response against recombinant tetravalent dengue antigen.

Nasal vaccine delivery systems are emerging alternatives to the conventional sub unit vaccine delivery systems owing to their ability to stimulate potent antigen specific humoral and cellular immune responses. Additional virtue of nasal delivery is its close proximity of immune cells to external epithelial layer which is the route of entry to pathogens. Toxicity of emulsion based vaccine delivery systems may be attributed to the presence of high quantities of surfactants used for stabilizing the emulsions.