Design and Synthesis of Benzimidazole Carboxamide Cysteine Protease Inhibitors as Promising Anti-leishmanial Agents.

Introduction: More than 20 protozoan species of Leishmania are responsible for causing Leishmaniasis, an infection spread by blood-feeding phlebotomine sandflies. A narrow pool of drugs is currently available rendering the current drug stratagem to treat this infection . Development of novel, less toxic, and more effective regimens is thus a need of the hour.

Design, synthesis, in vitro antiproliferative evaluation and GSK-3β kinase inhibition of a new series of pyrimidin-4-one based amide conjugates.

A new series of novel amide conjugates of pyrimidin-4-one and aromatic/heteroaromatic /secondary cyclic amines has been synthesized and their in vitro antiproliferative activities against a panel of 60 human cancer cell lines of nine different cancer types were tested at NCI. Among the synthesized compounds, compound (4i) showed significant anti-proliferative activity. Compound (4i) displayed most potent activity against the breast tumor cell line T-47D and CNS tumor cell line SNB-75 exhibiting a growth of 1.

Nanotechnology-based approaches applied to nutraceuticals.

Nutraceuticals and food industries are opening to a tremendously upcoming technology in the field of "Nano science". A new prospect has been defined by nanotechnology by conferring modified properties of nanomaterials and its application in the development of nanoformulations, nutritional supplements and food industry. Nanomaterials reveal exclusive properties because of their small size and high surface/volume ratio; thus, they have a complete application in nutraceuticals and food sector.

In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold.

Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site.

Design, synthesis and biological evaluation of benzoxazolinone-containing 1,3,4-thiadiazoles as TNF-α inhibitors.

A library of nineteen benzoxazolinone-based 1,3,4-thiadiazoles has been synthesized and screened for their anti-inflammatory activity. The compound exhibited a potent anti-inflammatory activity with an inhibition of 65.83% and 32.

Chemical constituents with antimicrobial and antioxidant activity from the aerial parts of (Sm.) Sweet.

(Sm.) Sweet grows all over the world and used to treat cough and bronchitis. The air-dried powder of the aerial parts was exhaustively extracted with methanol and the concentrated extract was adsorbed on silica gel for preparation of slurry.

Synthesis of benzimidazole-linked-1,3,4-oxadiazole carboxamides as GSK-3β inhibitors with in vivo antidepressant activity.

Recent findings of potential implications of glycogen synthase kinase-3β (GSK-3β) dysfunction in psychiatric disorders like depression, have increased focus for development of GSK-3β inhibitors with possible anti-depressant activity. Keeping this in view, we synthesized a series of benzimidazole-linked-1,3,4-oxadiazole carboxamides and evaluated them for in vitro GSK-3β inhibition. Active compounds were investigated for in vivo antidepressant activity in Wistar rats.

Oxazolo[4,5-b]pyridine-Based Piperazinamides as GSK-3β Inhibitors with Potential for Attenuating Inflammation and Suppression of Pro-Inflammatory Mediators.

Recent studies reveal that glycogen synthase kinase-3β (GSK-3β) acts as a pro-inflammatory enzyme, and by inhibiting this kinase, inflammation can be controlled. In this regard, a series of 17 piperazine-linked oxazolo[4,5-b]pyridine-based derivatives was synthesized and evaluated for in vitro GSK-3β inhibitory and in vivo anti-inflammatory activity. The compounds 7d, 7e, 7g, and 7c displayed the best GSK-3β inhibitory activity among all the synthesized compounds, with corresponding IC values of 0.

Novel 2,4-dichlorophenoxy acetic acid substituted thiazolidin-4-ones as anti-inflammatory agents: Design, synthesis and biological screening.

A library of fourteen 2-imino-4-thiazolidinone derivatives (1a-1n) has been synthesized and evaluated for in vivo anti-inflammatory activity and effect on ex-vivo COX-2 and TNF-α expression. Compounds 1k (5-(2,4-dichloro-phenooxy)-acetic acid (3-benzyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) and 1m (5-(2,4-dichloro-phenooxy)-acetic acid (3-cyclohexyl-4-oxo-thiazolidin-2-ylidene)-hydrazide) exhibited in vivo inhibition of 81.14% and 78.

Natural and synthetic bioactive inhibitors of glycogen synthase kinase.

Glycogen synthase kinase-3 is a multi-functional serine-threonine kinase and is involved in diverse physiological processes, including metabolism, cell cycle, and gene expression by regulating a wide variety of known substrates like glycogen synthase, tau-protein and β-catenin. Aberrant GSK-3 has been involved in diabetes, inflammation, cancer, Alzheimer's and bipolar disorder. In this review, we present an overview of the involvement of GSK-3 in various signalling pathways, resulting in a number of adverse pathologies due to its dysregulation.

Synthesis and immunopotentiating activity of novel isoxazoline functionalized coumarins.

A novel series (13) of isoxazoline functionalized coumarins was synthesized through 1,3-dipolar cyclization of nitrile oxides with Allylated coumarins. Synthesis of effective and target selective immunostimulators through conjugation of diversely substituted isoxazolines and 7-hydroxycoumarins is the focus of the present article. The proposed synthetic scheme was observed to be highly regiospecific yielding attempted conjugates in good yield (>90%).

Synthesis of pyrimidin-4-one-1,2,3-triazole conjugates as glycogen synthase kinase-3β inhibitors with anti-depressant activity.

GSK-3 specific inhibitors are promising candidates for the treatment of devastating pathologies such as diabetes, neurodegenerative diseases and cancers. We have synthesized a library of pyrimidin-4-one-1,2,3-triazole conjugates using click-chemistry approach and evaluated them as glycogen synthase kinase-3β inhibitors. Compounds 3g, 3j, 3n and 3r were found to be most potent among the eighteen pyrimidin-4-one-1,2,3-triazole conjugates synthesized and they were further evaluated for their in vivo anti-depressant activity.

Synthesis of benzimidazole based thiadiazole and carbohydrazide conjugates as glycogen synthase kinase-3β inhibitors with anti-depressant activity.

A series of benzimidazole based thiadiazole and carbohydrazide conjugates have been synthesized and evaluated for inhibition of glycogen synthase kinase-3β and anti-depressant effect. Compounds 4f, 4j, 5b, 5g and 5i were found to be the most potent inhibitors of GSK-3β in vitro amongst the twenty-five benzimidazole based thiadiazole and carbohydrazide conjugates synthesized. Compound 5i was also found to exhibit significant antidepressant activity in vivo at 50mg/kg, when compared to fluoxetine, a known antidepressant drug.

Novel Piperine Derivatives with Antidiabetic Effect as PPAR-γ Agonists.

Piperine is an alkaloid responsible for the pungency of black pepper. In this study, piperine isolated from Piper nigrum L. was hydrolyzed under basic condition to obtain piperic acid and was used as precursor to carry out the synthesis of twenty piperine derivatives containing benzothiazole moiety.

Synthesis of Novel Oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles as Glycogen Synthase Kinase-3β Inhibitors with Anti-inflammatory Potential.

A novel series of oxazolo[4,5-b]pyridine-2-one based 1,2,3-triazoles has been synthesized by click chemistry approach and evaluated for in vitro GSK-3β inhibitory activity. Compound 4g showed maximum inhibition with IC50 value of 0.19 μm.

Recent trends in electrospinning of polymer nanofibers and their applications in ultra thin layer chromatography.

Fabrication of polymer derived electrospun nanofibers by electrospinning as chromatographic sorbent bed for ultra-thin layer chromatography (UTLC) is a very demanding topic in analytical chemistry. This review presents an overview of recent development in the fabrication of polymer derived electrospun nanofibers and their applications to design UTLC plates as stationary phases for on-plate identification and separation of analytes from their mixture solutions. It has been reported that electrospun fiber based stationary phases in UTLC have enhanced separation efficiency to provide separation of analyte mixture in a shorter development time than those of traditional particle-based TLC stationary phases.

Synthesis and tyrosinase inhibition activity of trans-stilbene derivatives.

Synthesis of a focussed library of trans-stilbene compounds through Wittig and other base catalysed condensation reactions is presented. The synthesized stilbenes were screened for their inhibitory potential against murine tyrosinase activity to explore the structure activity relationship (SAR). Presence of electron withdrawing group (-CN) at the double bond and hydroxyl group or halogen atom especially at para-position on the aromatic rings was found to significantly elevate the inhibitory activity.

Synthesis of Novel Pyrimidin-4-One Bearing Piperazine Ring-Based Amides as Glycogen Synthase Kinase-3β Inhibitors with Antidepressant Activity.

Novel pyrimidin-4-one derivatives have been synthesized using EDC coupling and evaluated as glycogen synthase kinase-3β (GSK-3β) inhibitors. Among all the synthesized compounds, compound 5 (3-methyl-6-phenyl-2-(piperazin-1-yl)-3,4-dihydropyrimidin-4-one) exhibited the most potent inhibitory activity against GSK-3β with IC50 value of 74 nm. The molecular docking studies were performed to elucidate the binding modes of the compounds with the target, and a crucial interaction involving hydrogen bond formation with Val-135 to the active site of GSK-3β was observed.

Antidiabetic effect of novel benzenesulfonylureas as PPAR-γ agonists and their anticancer effect.

Twenty one pyrazoline containing benzenesulfonylureas were synthesized and docked against PPAR-γ target. All the compounds were first screened for their antidiabetic potential by oral glucose tolerance test and then six active compounds were assessed on STZ diabetic model. It was found that five compounds showed significantly high antidiabetic activity in comparison to glibenclamide as well as rosiglitazone (standard drugs).

Design, Synthesis, and Biological Evaluation of Thiazolidine-2,4-dione Conjugates as PPAR-γ Agonists.

A library of synthesized conjugates of phenoxy acetic acid and thiazolidinedione 5a-m showed potent peroxisome proliferator activated receptor-γ (PPAR-γ) transactivation as well as significant blood glucose lowering effect comparable to the standard drugs pioglitazone and rosiglitazone. Most of the compounds showed higher docking scores than the standard drug rosiglitazone in the molecular docking study. Compounds 5l and 5m exhibited PPAR-γ transactivation of 54.

Synthesis, biological evaluation and molecular docking of some substituted pyrazolines and isoxazolines as potential antimicrobial agents.

A series of substituted pyrazolines (2a-e, 3a-h and 6a-c) and isoxazolines (4a-e) were synthesized and their structures were established on the basis of IR, (1)H NMR, (13)C NMR and mass spectra. All the synthesized compounds were tested against two bacterial and four fungal strains and found to exhibit moderate to potent antifungal activity. Compounds 2b, 4c, 4d and 6a-c exhibited significant activity against all tested fungal strains.

Ameliorative effects of Trichosanthes dioica Extract in suppressing inflammatory mediators and attenuating oxidative stress.

The present study aimed to investigate the anti-inflammatory activity of the ethanolic extract of the aerial parts of Trichosanthes dioica and its successive fractions. The effect on oxidative stress involved in the pathogenesis of inflammation was evaluated. The ethanolic extract and its successive fractions were administered at a dose of 150 and 300 mg/kg b.

Design and Synthesis of Butenolide-based Novel Benzyl Pyrrolones: Their TNF-α based Molecular Docking with In vivo and In vitro Anti-inflammatory Activity.

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF-α target. Among all the docked molecules, compound 3f showed best glide score of -6.89.

Design, synthesis and biological evaluation of piperic acid triazolyl derivatives as potent anti-inflammatory agents.

Nineteen novel piperine based triazoles have been synthesized using click chemistry approach and were tested for in vivo anti-inflammatory activity. The most active compounds were evaluated for in vitro TNF-α expression. Compounds 3g and 3f were found to show significant in vivo inhibition of inflammation, 80.

1,3,4-Thiadiazoles: a potent multi targeted pharmacological scaffold.

Despite a significant work on thiadiazoles, continuous efforts are still being made to identify novel heterocyclic compounds with potent biological activities. This review may help the medicinal chemists to develop new leads possessing 1,3,4-thiadiazole nucleus with higher efficacy and reduced side effects. This review throws light on the detailed synthetic approaches which have been used for the synthesis of thiadiazoles.