Synthesis, and evaluation of α-amylase and α-glucosidase inhibitory potential of new pyrazolo[3,4-d]pyrimidine derivatives

A series of new pyrazolo[3,4-d]pyrimidine compounds were synthesized in excellent yields via sulfuration and 1,3-dipolar cycloaddition and confirmed by MS, FT-IR and NMR techniques. All the prepared compounds were screened in vitro for their α-amylase and α-glucosidase inhibitory activities. Preliminary results indicated that some target compounds exhibited promising α-amylase and α-glucosidase inhibitory activity potency. Among the tested products, the cycloadduct f was found most active inhibitor (IC50 = 134.30 μM) for α-amylase, and the sulphur product b is the most active inhibitor (IC50 = 16.37 μM) for α-glucosidase

t-DARPP regulates phosphatidylinositol-3-kinase-dependent cell growth in breast cancer

<p>Abstract</p> <p>Background</p> <p>Recent reports have shown that t-DARPP (truncated isoform of DARPP-32) can mediate trastuzumab resistance in breast cancer cell models. In this study, we evaluated expression of t-DARPP in human primary breast tumors, and investigated the role of t-DARPP in regulating growth and proliferation in breast cancer cells.</p> <p>Results</p> <p>Quantitative real time RT-PCR analysis using primers specific for t-DARPP demonstrated overexpression of t-DARPP in 36% of breast cancers (13/36) as opposed to absent to very low t-DARPP expression in normal breast tissue (p < 0.05). The mRNA overexpression of t-DARPP was overwhelmingly observed in ductal carcinomas, including invasive ductal carcinomas and intraductal carcinomas, rather than other types of breast cancers. The immunohistochemistry analysis of DARPP-32/t-DARPP protein(s) expression in breast cancer tissue microarray that contained 59 tumors and matched normal tissues when available indicated overexpression in 35.5% of primary breast tumors that were more frequent in invasive ductal carcinomas (43.7%; 21/48). In vitro studies showed that stable overexpression of t-DARPP in MCF-7 cells positively regulated proliferation and anchorage-dependent and -independent growth. Furthermore, this effect was concomitant with induction of phosphorylation of AKT^ser473and its downstream target phospho^ser9GSK3β, and increased Cyclin D1 and C-Myc protein levels. The knockdown of endogenous t-DARPP in HCC1569 cells led to a marked decrease in phosphorylation of AKTs^ser473and GSK3β^ser9. The use of PI3K inhibitor LY294002 or Akt siRNA abrogated the t-DARPP-mediated phosphorylation of AKT^ser473and led to a significant reduction in cell growth.</p> <p>Conclusions</p> <p>Our findings underscore the potential role of t-DARPP in regulating cell growth and proliferation through PI3 kinase-dependent mechanism.</p

Inventory of poisonings and toxicological studies carried out on Atractylis gummifera L.: A review

Atractylis gummifera L. belongs to the family Asteraceae is widely used in traditional Moroccan medicine for its therapeutic effects (diuretic, purgative, emetic, abortive), but it causes serious and fatal poisonings, hence the objective of this work is to describe the current state of intoxication caused by A. gummifera in the Mediterranean and to summarize the toxicological studies carried out on this plant. The working methodology we adopted consisted in collecting data published in Arabic, French and English in specialized articles, books and on websites. Research results showed that the Centre Anti Poison and Pharmacovigilance of Morocco declared A. gummifera was in second place in the occurrence of poisonings in between January 1980 and December 2008. The synthesis of experimental work on plant toxicology showed that the lethal dose of A. gummifera varies according to the animal model used (rat or mouse), the route of administration (intraperitoneal, oral or intravenous) and the part of the plant used. The root has been found to be the most toxic part of the plant. The toxicity of A. gummifera is due to atractyloside and gummiferine, which are inhibitors of oxidative phosphorylation that prevent the formation of ATP from ADP in intracellular organelles. This study shows the interest in raising public awareness of the toxicity of A. gummifera and in rationalizing its use in traditional medicine

In vivo anti-diabetic effect of aqueous and methanolic macerated extracts of Atractylis gummifera

The anti-diabetic effect of Atractylis gummifera (plant used in traditional Moroccan medicine) has been evaluated in type 2 diabetic mice model. The mice were divided into five groups: Normal control, diabetic control, diabetic treated with aqueous macerate (500 mg/kg), diabetic treated with methanol macerate (500 mg/kg) and diabetic treated with metformin (300 mg/kg). The treatment of the mice was performed by daily gastric gavage for 5 weeks. The monitoring of the mice was carried out weekly by fasting glucose and measurement of biochemical parameters at the end of treatment. The aqueous macerate of A. gummifera was most effective that reduced the fasting blood glucose with 62.7%. In addition, this extract restored the biochemical parameters of diabetic mice to normal