Design, synthesis and anticancer activity of N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives.

Novel N-(1-(4-(dibenzo[b,f][1,4]thiazepin-11-yl)piperazin-1-yl)-1-oxo-3-phenylpropan-2-yl derivatives were designed, synthesized and their chemical structures were confirmed by 1H NMR, 13C NMR and Mass spectra. The anticancer activities of the newly synthesized compounds were evaluated in vitro against three human cancer cell lines including K562, Colo-205 and MDA-MB 231 by MTT assay. The screening results showed that five compounds (16b, 16d, 16i, 16p and 16q) exhibited potent cytotoxic activities with IC50 values between 20 and 40µM. Further in vitro studies revealed that inhibition of sirtuins could be the possible mechanism of action of these molecules.

Effects of a Proprietary Standardized Orthosiphon stamineus Ethanolic Leaf Extract on Enhancing Memory in Sprague Dawley Rats Possibly via Blockade of Adenosine A 2A Receptors.

The aim of the study was to explore a propriety standardized ethanolic extract from leaves of Orthosiphon stamineus Benth in improving impairments in short-term social memory in vivo, possibly via blockade of adenosine A2A receptors (A2AR). The ethanolic extract of O. stamineus leaves showed significant in vitro binding activity of A2AR with 74% inhibition at 150 µg/ml and significant A2AR antagonist activity with 98% inhibition at 300 µg/mL. A significant adenosine A1 receptor (A1R) antagonist activity with 100% inhibition was observed at 300 µg/mL. Its effect on learning and memory was assessed via social recognition task using Sprague Dawley rats whereby the ethanolic extract of O. stamineus showed significant (p < 0.001) change in recognition index (RI) at 300 mg/kg and 600 mg/kg p.o and 120 mg/kg i.p., respectively, compared to the vehicle control. In comparison, the ethanolic extract of Polygonum minus aerial parts showed small change in inflexion; however, it remained insignificant in RI at 200 mg/kg p.o. Our findings suggest that the ethanolic extract of O. stamineus leaves improves memory by reversing age-related deficits in short-term social memory and the possible involvement of adenosine A1 and adenosine A2A as a target bioactivity site in the restoration of memory.

Phyllanthus maderaspatensis, a dietary supplement for the amelioration of adriamycin-induced toxicity and oxidative stress in mice.

The effect of ethanol extract of Phyllanthus maderaspatensis (PME), a popular south Indian dietary supplement, was studied for its chemoprotective property on adriamycin (ADR)-induced toxicity and oxidative stress in mice. Adriamycin toxicity was evaluated biochemically by measuring the serum concentration of lactate dehydrogenase (LDH) and creatinine phosphokinase (CPK). Genotoxicity was evaluated by measuring the frequency of micronucleated polychromatic erythrocytes (MNPCEs) in bone marrow cells. Oxidative stress in the heart tissue was estimated by measuring the glutathione (GSH) levels in the homogenate. The treatment of mice with different doses of PME (400 mg/kg and 600 mg/kg body weight, p.o.,) for 7 days before the administration of a single i.p. dose of ADR (15 mg/kg) exhibited significant protection in a dose-dependent manner. The results clearly indicate that PME has a protective effect against ADR-induced toxicity, as revealed by the decrease in the concentrations of LDH, CPK, and the frequency of MNPCEs. The increased levels of GSH are indicative of the antioxidant property of PME.

Effect of lupeol isolated from Crataeva nurvala Buch.-Ham. stem bark extract against free radical induced nephrotoxicity in rats.

Lupeol, isolated from Crataeva nurvala stem bark in doses 40 and 80 mg/kg body weight, po, for 10 days, decreased the concentration of blood urea nitrogen, creatinine and lipid peroxidation and increased glutathione and catalase activities in cisplatin (5 mg/kg body weight, ip) induced nephrotoxicity in rats. The increased glutathione and catalase activities are indicative of antioxidant properties of lupeol.