Prem P. Yadav

Cassane Diterpenes from Caesalpinia bonduc.

Three cassane diterpene hemiketals, caesalpinolide-C, caesalpinolide-D, caesalpinolide-E and one cassane furanoditerpene were isolated from Caesalpinia bonduc. The molecular structures were elucidated using NMR spectroscopy in combination with IR, UV and mass spectral data and relative stereochemistries were determined through ROESY correlation. The isolated compounds were tested for their antiproliferative activity against MCF-7 (breast adenocarcinoma), DU145 (prostate carcinoma), C33A (Cervical carcinoma) and Vero (African green monkey kidney fibroblast) cells.

Antiproliferative action of Xylopia aethiopica fruit extract on human cervical cancer cells.

The anticancer potential of Xylopia aethiopica fruit extract (XAFE), and the mechanism of cell death it elicits, was investigated in various cell lines. Treatment with XAFE led to a dose‐dependent growth inhibition in most cell lines, with selective cytotoxicity towards cancer cells and particularly the human cervical cancer cell line C‐33A. In this study, apoptosis was confirmed by nuclear fragmentation and sub‐G0/G1 phase accumulation. The cell cycle was arrested at the G2/M phase with a decreased G0/G1 population. A semi‐quantitative gene expression study revealed dose‐dependent up‐regulation of p53 and p21 genes, and an increase in the Bax/Bcl‐2 ratio. These results indicate that XAFE could be a potential therapeutic agent against cancer since it inhibits cell proliferation, and induces apoptosis and cell cycle arrest in C‐33A cells. Copyright

Identification of pongamol and karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits

AIM OF THE STUDY To identify pongamol and karanjin as lead compounds with antihyperglycemic activity from Pongamia pinnata fruits. MATERIAL AND METHODS Streptozotocin-induced diabetic rats and hyperglycemic, hyperlipidemic and hyperinsulinemic db/db mice were used to investigate the antihyperglycemic activity of pongamol and karangin isolated from the fruits of Pongamia pinnata. RESULTS In streptozotocin-induced diabetic rats, single dose treatment of pongamol and karanjin lowered the blood glucose level by 12.8% (p<0.05) and 11.7% (p<0.05) at 50mg /kg dose and 22.0% (p<0.01) and 20.7% (p<0.01) at 100mg/kg dose, respectively after 6h post-oral administration. The compounds also significantly lowered blood glucose level in db/db mice with percent activity of 35.7 (p<0.01) and 30.6 (p<0.01), respectively at 100mg/kg dose after consecutive treatment for 10 days. The compounds were observed to exert a significant inhibitory effect on enzyme protein tyrosine phosphatase-1B (EC 3.1.3.48). CONCLUSION The results showed that pongamol and karangin isolated from the fruits of Pongamia pinnata possesses significant antihyperglycemic activity in Streptozotocin-induced diabetic rats and type 2 diabetic db/db mice and protein tyrosine phosphatase-1B may be the possible target for their activity.

A review on cassane and norcassane diterpenes and their pharmacological studies

The natural Cassane and norcassane diterpenes are biosynthetic rearrangement products of Pimarane precursor in the biosynthetic pathway of diterpenes. Their distribution is highly restricted to various genera of Fabaceae family (especially to Caesalpinia genus). A comprehensive account of the structural diversity (322 structures, 114 references) is given in this review along with biological activities of cassane and norcassane diterpenes up to September 2011.

Pongamol from Pongamia pinnata stimulates glucose uptake by increasing surface GLUT4 level in skeletal muscle cells.

Skeletal muscle is the major site of postprandial glucose disposal and augmenting glucose uptake into this tissue may attenuate insulin resistance that precedes type 2 diabetes mellitus. Here, we investigated the effect of pongamol, an identified lead molecule from the fruits of Pongamia pinnata, on glucose uptake and GLUT4 translocation in skeletal muscle cells. In L6-GLUT4myc myotubes treatment with pongamol significantly promoted both glucose transport and GLUT4 translocation to the cell surface in a concentration-dependent manner, without changing the total amount of GLUT4 protein and GLUT4 mRNA, effects that were also additive with insulin. Cycloheximide treatment inhibited the effect of pongamol on GLUT4 translocation suggesting the requirement of new protein synthesis. The pongamol-induced increase in GLUT4 translocation was completely abolished by wortmannin, and pongamol significantly potentiated insulin-mediated phosphorylation of AKT (Ser-473). We conclude that pongamol-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane, driven by a PI-3-K/AKT dependent mechanism.

Transition-Metal-Free C-3 Arylation of Quinoline-4-ones with Arylhydrazines.

A transition-metal-free C-3-arylation of quinolin-4-ones in the presence of base has been achieved by using arylhydrazines as aryl radical source and air as oxidant. The reaction proceeds smoothly at room temperature and does not require any prefunctionalization and N-protection of quinoline-4-ones. The utility of this methodology is further demonstrated in synthesis of quinoline-quinolone hybrid as well as 6-aryl-benzofuro[3,2-c]quinoline scaffold.

Synthesis of 4-hydroxy-1-methylindole and benzo[b]thiophen-4-ol based unnatural flavonoids as new class of antimicrobial agents ☆

Abstract Synthesis of nitrogen and sulfur heterocyclic mimics of furanoflavonoids have been achieved for the first time. Synthesized flavonoid alkaloids and thiophenyl flavonoids have been screened for antifungal and antibacterial activities. All the test compounds barring 25 exhibited antifungal activity. The compound 19 was the best and showed comparable MICs to the known compound karanjin. Compounds 5, 12, 14 and 22 also showed comparable MIC to karanjin.

Copper-catalyzed highly efficient oxidative amidation of aldehydes with 2-aminopyridines in an aqueous micellar system

An environmentally benign protocol for the synthesis of N-(pyridine-2-yl)amides from aldehydes and 2-aminopyridines has been developed under mild reaction conditions. This approach requires Cu(OTf)2 as a catalyst, and inexpensive molecular iodine as an oxidant under anionic micellar catalysis in aqueous medium at room temperature.

Regioselective α-arylation of coumarins and 2-pyridones with phenylhydrazines under transition-metal-free conditions

A facile regioselective metal-free direct α-arylation of coumarins and 2-pyridones is achieved by the reaction of coumarins and 2-pyridones with phenylhydrazine in good yields. The reaction proceeds at room temperature under mild conditions using inexpensive reagents and without the need for step intensive activating groups. The methodology is operationally simple, practically viable and also allows the coupling of similar nitrogen heterocycle aza-coumarins without prerequisite N-protection.

Karanjin from Pongamia pinnata induces GLUT4 translocation in skeletal muscle cells in a phosphatidylinositol-3-kinase-independent manner

Insulin-stimulated glucose uptake in skeletal muscle is decreased in type 2 diabetes due to impaired translocation of insulin-sensitive glucose transporter 4 (GLUT4) from intracellular pool to plasma membrane. Augmenting glucose uptake into this tissue may help in management of type 2 diabetes. Here, the effects of an identified antihyperglycemic molecule, karanjin, isolated from the fruits of Pongamia pinnata were investigated on glucose uptake and GLUT4 translocation in skeletal muscle cells. Treatment of L6-GLUT4myc myotubes with karanjin caused a substantial increase in the glucose uptake and GLUT4 translocation to the cell surface, in a concentration-dependent fashion, without changing the total amount of GLUT4 protein and GLUT4 mRNA. This effect was associated with increased activity of AMP-activated protein kinase (AMPK). Cycloheximide treatment inhibited the effect of karanjin on GLUT4 translocation suggesting the requirement of de novo synthesis of protein. Karanjin-induced GLUT4 translocation was further enhanced with insulin and the effect is completely protected in the presence of wortmannin. Moreover, karanjin did not affect the phosphorylation of AKT (Ser-473) and did not alter the expression of the key molecules of insulin signaling cascade. We conclude that karanjin-induced increase in glucose uptake in L6 myotubes is the result of an increased translocation of GLUT4 to plasma membrane associated with activation of AMPK pathway, in a PI-3-K/AKT-independent manner.