A tuning fork-shaped bisbenzothiazole derivative as a pH-responsive digital fluorescent probe and its evaluation.

A new highly emissive pH-responsive near-IR active digital probe was designed and synthesized. The probe is based on a bisbenzothiazole motif with a highly vulnerable hydrogen unit attached in an intramolecular fashion. The probe produced a large Stokes shift which was observed to be highly pH dependent.

In the Quest for Potent and Selective Malic Enzyme 3 Inhibitors for the Treatment of Pancreatic Ductal Adenocarcinoma.

The genome of pancreatic ductal adenocarcinoma (PDAC) is associated with frequent deletion of the tumor suppressor gene SMAD family member 4 () with collateral deletion of its chromosomal neighbor malic enzyme 2 (). In PDAC cells, ME3 takes over the function of the ME2 enzyme, and hence therapeutic targeting of ME3 is expected to arrest tumor growth. Hitherto no selective small molecule inhibitor of ME3 has been reported in the context of PDAC.

Neuroprotective effects of quercetin produced by an endophytic fungus Nigrospora oryzae isolated from Tinospora cordifolia.

Aims: Alzheimer's disease is considered one of the most prevalent neurodegenerative disorders and dementia is the core symptom of this disease. This study was aimed to test the bioactive compounds produced by endophytic fungus for the inhibition of acetylcholinesterase (AChE) activity and to identify the compound responsible for this activity.

Methods And Results: Endophytic fungi were isolated from the medicinal plant Tinospora cordifolia and screened for AChE inhibition and antioxidant activity.

Evaluation of enzyme and microwave-assisted conditions on extraction of anthocyanins and total phenolics from black soybean (Glycine max L.) seed coat.

The present study compares three methods viz. microwave-assisted extraction (MAE), enzyme-assisted extraction (EAE) and conventional solvent extraction (CSE) for extraction of polyphenolic compounds from Black Soybean Seed coat (BSSC). Box-Behnken design using response surface methodology (RSM) was employed to investigate and optimize the MAE and EAE for maximum bioactive content, antioxidant activity, colour density and minimum degradation parameters from BSSC.

Valorisation of black carrot pomace: microwave assisted extraction of bioactive phytoceuticals and antioxidant activity using Box-Behnken design.

The present study compares three methods viz. microwave assisted extraction (MAE), ultrasonic-assisted extraction (UAE) and conventional solvent extraction (CSE) for extraction of phenolic compounds from black carrot pomace (BCP). BCP is the major by-product generated during processing and poses big disposal problem.

Current Perspectives on Novel Drug Carrier Systems and Therapies for Management of Pancreatic Cancer: An Updated Inclusive Review.

Pancreatic cancer (PC) is one of the most fatal solid tumors, resulting in more than 250,000 deaths per year globally. It is the eighth leading cause of death from cancer in men and women throughout the world and is now third leading cause of cancer-related deaths in the United States. In addition, the worldwide occurrence of PC ranges from 1 to 10 cases per 100,000 people, indicating a higher incidence in developed countries.

Discovery of a Potent and Orally Efficacious TGR5 Receptor Agonist.

TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The 2-thio-imidazole derivative 6g was identified as a novel, potent, and selective TGR5 agonist (hTGR5 EC50 = 57 pM, mTGR5 = 62 pM) with a favorable pharmacokinetic profile. The compound 6g was found to have potent glucose lowering effects in vivo during an oral glucose tolerance test in DIO C57 mice with ED50 of 7.

Gastroprotective activity of polyphenolic-rich extract of Potentilla mooniana.

Context: Potentilla mooniana Wight. (Rosaceae) is a plant found in the Himalayan region where the root is traditionally used to treat stomach problems including gastric-ulcer.

Objective: To scientifically validate the gastro-protective effect and derive the possible mechanistic activity of the ethanol root extract from P.

Design, synthesis and biological evaluation of novel aminomethyl-piperidones based DPP-IV inhibitors.

A series of novel aminomethyl-piperidones were designed and evaluated as potential DPP-IV inhibitors. Optimized analogue 12v ((4S,5S)-5-(aminomethyl)-1-(2-(benzo[d][1,3]dioxol-5-yl)ethyl)-4-(2,5-difluorophenyl)piperidin-2-one) showed excellent in vitro potency and selectivity for DPP-IV over other serine proteases. The lead compound 12v showed potent and long acting antihyperglycemic effects (in vivo), along with improved pharmacokinetic profile.

Hybanthus enneaspermus (L.) F. Muell: a concise report on its phytopharmacological aspects.

Hybanthus enneaspermus (L.) F. Muell belonging to the family Violaceae, popularly known as Ratanpurus (Hindi) is a herb or a shrub distributed in the tropical and subtropical regions of the world.

Synthesis and structure-activity relationship of potent, selective and orally active anthranilamide-based factor Xa inhibitors: application of weakly basic sulfoximine group as novel S4 binding element.

A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2-(diethylamino)acetyl)-S-methylsulfonimidoyl)benzamido)benzamide (18f).

Peptidomimetics as potent and selective PTP1B inhibitors.

A series of peptidomimetic containing bidentate pTyr mimetics (9a-w) are reported as potent and selective PTP1B inhibitors. Compounds (9p and 9q) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro), which confirms discovery of highly potent and selective PTP1B inhibitors.

Discovery of liver selective non-steroidal glucocorticoid receptor antagonist as novel antidiabetic agents.

Series of benzyl-phenoxybenzyl amino-phenyl acid derivatives (8a-q) are reported as non-steroidal GR antagonist. Compound 8g showed excellent h-GR binding and potent antagonistic activity (in vitro). The lead compound 8g exhibited significant oral antidiabetic and antihyperlipidemic effects (in vivo), along with liver selectivity.

Prosopis cineraria: a potential nootropic agent.

Context: Prosopis cineraria (L.) Druce (Leguminosae), a plant of the Thar Desert of India and Pakistan is used traditionally by local people for the treatment of memory disorders and to arrest wandering of the mind.

Objective: The study includes scientific validation of P.

Percutaneous nephrolithotomy and chronic kidney disease: results from the CROES PCNL Global Study.

Purpose: We compared the characteristics and outcomes of patients treated with percutaneous nephrolithotomy in the CROES (Clinical Research Office of the Endourological Society) Global Study according to preoperative renal function.

Materials And Methods: Prospective data on consecutive patients treated with percutaneous nephrolithotomy in a 1-year period were collected from 96 participating centers. The glomerular filtration rate was estimated using the Modification of Diet in Renal Disease formula based on preoperative serum creatinine measurement.

Long-acting peptidomimetics based DPP-IV inhibitors.

Pyrrolidine based peptidomimetics are reported as potent and selective DPP-IV inhibitors for the treatment of T2DM. Compounds 16c and 16d showed excellent in vitro potency and selectivity towards DPP-IV and the lead compound 16c showed sustained antihyperglycemic effects, along with improved pharmacokinetic profile.

Evaluation of in vitro aldose reductase inhibitory potential of different fraction of Hybanthus enneaspermus Linn F. Muell.

Objective: To evaluate the aldose reductase inhibitory (ARI) activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract.

Methods: Total phenol and flavonoid content of different fractions was determined. ARI activity of different fractions in rat lens was investigated in vitro.

Discovery of potent, selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors.

A novel series of pTyr mimetics containing triaryl-sulfonamide derivatives (5a-r) are reported as potent and selective PTP1B inhibitors. Some of the test compounds (5o and 5p) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro). The lead compound 5o showed potent antidiabetic activity (in vivo), along with improved pharmacokinetic profile.

Antidiabetic activity of alcoholic leaves extract of Alangium lamarckii Thwaites on streptozotocin-nicotinamide induced type 2 diabetic rats.

Objective: To investigate antidiabetic potential of alcoholic leaves extract of Alangium lamarckii (A. lamarckii) on streptozotocin-nicotinamide induced type 2 diabetic rats.

Methods: Oral glucose tolerance test was done by inducing hyperglycemic state via administration of glucose in water (2g/kg).

Inhibitory effect of two Indian medicinal plants on aldose reductase of rat lens in vitro.

Objective: To assesse the inhibitory effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and, Alangium lamarckii Thwaits on aldose reductase (AR) of rat lens.

Methods: Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content.

Results: The alcoholic extract of Ceasalpinia digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme.

Discovery of inhibitors of plasminogen activator inhibitor-1: structure-activity study of 5-nitro-2-phenoxybenzoic acid derivatives.

Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as potent PAI-1 inhibitors using hybridization and conformational restriction strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a, 6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral bioavailability in the rodents.

Antidiabetic and in vitro antioxidant potential of Hybanthus enneaspermus (Linn) F. Muell in streptozotocin-induced diabetic rats.

Objective: To evaluate antidiabetic and antioxidant potential of Hybanthus enneaspermus in different models.

Methods: The oral glucose tolerance test (OGTT) and normoglycemic effect of alcoholic extract of Hybanthus enneaspermus (AHE) were evaluated at a dose of 125, 250 and 500 mg/kg p.o.