Design, synthesis and biological evaluation of some tetrazole acetamide derivatives as novel non-carboxylic PTP1B inhibitors.

A series of ten N-(3-(1H-tetrazole-5-yl)phenyl)acetamide derivatives (NM-07 to NM-16) designed from a lead molecule identified previously in our laboratory were synthesized and evaluated for protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Among the synthesized molecules, NM-14, a 5-Cl substituted benzothiazole analogue elicited significant PTP1B inhibition with an IC of 1.88 µM against reference standard suramin (IC ≥ 10 µM).

Synthesis and biological evaluation of some N-(3-(1H-tetrazol-5-yl) phenyl)acetamide derivatives as novel non-carboxylic PTP1B inhibitors designed through bioisosteric modulation.

Described herein is the synthesis and biological evaluation of a series of non-carboxylic inhibitors of Protein Tyrosine Phosphatase 1B designed using bioisosteric replacement strategy. Six N-(3-(1H-tetrazol-5-yl)phenyl)acetamide derivatives designed employing the aforementioned strategy were synthesized and screened for PTP1B inhibitory activity. Among the synthesized compounds, compound NM-03 exhibited the most potent inhibitory activity with IC value of 4.

Design, synthesis and anti-diabetic activity of triazolotriazine derivatives as dipeptidyl peptidase-4 (DPP-4) inhibitors.

Type 2 diabetes mellitus (T2DM) is one of the major global metabolic disorders characterized by insulin resistance and chronic hyperglycemia. Inhibition of the enzyme, dipeptidyl peptidase-4 (DPP-4) has been proved as successful and safe therapy for the treatment of T2DM since last decade. In order to design novel DPP-4 inhibitors, various in silico studies such as 3D-QSAR, pharmacophore modeling and virtual screening were performed and on the basis of the combined results of them, total 50 triazolo[5,1-c][1,2,4]triazine derivatives were designed and mapped on the best pharmacophore model.

Protective effect of Tephrosia purpurea in diabetic cataract through aldose reductase inhibitory activity.

Purpose: Tephrosia purpurea (T. purpurea) has been reported to prevent cataract formation in senile cataract model as well as proven effective in STZ induced type 1 diabetes. Aldose reductase (AR) is a key enzyme in the intracellular polyol pathway responsible for the development of diabetic cataract.

Effect of flavonoid rich fraction of Tephrosiapurpurea (Linn.) Pers. on complications associated with streptozotocin-induced type I diabetes mellitus.

Globally, diabetes is a serious health issue affecting one in 11 adults and consumes 12% of global health expenditure. Prevalence of dyslipidemia in diabetes is not uncommon since decades. Further, patients with type II diabetes have 2-4 folds more risk for cardiovascular disease (CVD).

Effect of Aqueous Extract of Tephrosia purpurea on Cardiovascular Complications and Cataract Associated with Streptozotocin-induced Diabetes in Rats.

Tephrosia purpurea has been reported to possess antidiabetic activity, however, its effects on cardiovascular complications and cataract associated with diabetes have not been studied. The objective of the present study was to investigate the effects of aqueous extract of Tephrosia purpurea on cardiovascular complications and cataract associated with streptozotocin-induced diabetes in rats. Sprague Dawley rats of either sex were made diabetic with streptozotocin (45 mg/kg, i.

Preventive Effect of Tephrosia purpurea on Selenite-Induced Experimental Cataract.

Purpose: Recent investigations have shown that phytochemical antioxidants can scavenge free radicals and prevent various diseases like cataract. The objective of the present study was to assess the efficacy of the Tephrosia purpurea in preventing these changes in the lens of selenite-induced cataract models.

Materials And Methods: Cataract was induced by a single injection of sodium selenite (4 mg/kg, s.

Type 2 diabetes-induced cardiovascular complications: comparative evaluation of spironolactone, atenolol, metoprolol, ramipril and perindopril.

The present study was carried out to study the effect of spironolactone, atenolol, metoprolol, ramipril and perindopril on cardiovascular complications in neonatal model of diabetes in rats, induced by administering 90 mg/kg streptozotocin (STZ), i.p. in 2-day-old rats.

Investigation of the potential effects of metformin on atherothrombotic risk factors in hyperlipidemic rats.

The increased mortality rate due to atherothrombotic events and related complications has necessitated the search for new pharmacological agents. Hyperlipidemia, thrombosis and oxidative stress are the primary underlying concerns in the pathogenesis of atherosclerosis. Metformin, although proved to be beneficial in micro and macrovascular complications of diabetes mellitus, its effects on pure cardiovascular subjects are still debatable.

β(3) Receptors: Role in Cardiometabolic Disorders.

Pharmacological and molecular approaches have shown that an atypical β-adrenoceptor (AR), called β(3)-AR, that is distinct from β(1)-ARs and β(2)-ARs, exists in some tissues in heterogeneous populations such as β(3a)-ARs and β(3b)-ARs. β(3)-ARs belong to a superfamily of receptors linked to guanine nucleotide binding proteins (G proteins). The β(3)-AR gene contains two introns whereas the β(1)-AR and β(2)-AR genes are intronless, leading to splice variants.

Angiogenic targets for potential disorders.

This review shall familiarize the readers with various fundamental aspects of angiogenesis. Angiogenesis is a feature of a limited number of physiological processes like wound healing, ovulation, development of the corpus luteum, embryogenesis, lactating breast, during immune response, and during Inflammation. It is driven by a cocktail of growth factors and pro-angiogenic cytokines and is tempered by an equally diverse group of inhibitors of neovascularization.

Therapeutic opportunities of small interfering RNA.

Formation of small interfering RNA (siRNA) occurs in two steps involving binding of the RNA nucleases to a large double-stranded RNA (dsRNA) and its cleavage into fragments called siRNA. In the second step, these siRNAs join a multinuclease complex, which degrades the homologous single-stranded mRNAs. The delivery of siRNA involves viral- and non-viral-mediated delivery systems; the approaches for chemical modifications have also been developed.

Getting into the brain: approaches to enhance brain drug delivery.

Being the most delicate organ of the body, the brain is protected against potentially toxic substances by the blood-brain barrier (BBB), which restricts the entry of most pharmaceuticals into the brain. The developmental process for new drugs for the treatment of CNS disorders has not kept pace with progress in molecular neurosciences because most of the new drugs discovered are unable to cross the BBB. The clinical failure of CNS drug delivery may be attributed largely to a lack of appropriate drug delivery systems.

Comparative evaluation of atenolol and metoprolol on cardiovascular complications associated with streptozotocin-induced diabetic rats.

Recently, various clinical studies have indicated that lipophilic beta-blockers reduce the coronary mortality in diabetic patients; however, systematic studies have not been reported. The objective of the present investigation was to compare the effects of chronic treatment with metoprolol and atenolol on cardiovascular complications in streptozotocin (STZ)-induced diabetic rats. Injection of STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, cardiac hypertrophy, reduction in heart rate, and structural alterations in cardiac tissues.