A new set of pyrazolo[3,4-d]pyrimidine and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidine scaffolds (4–13) as well as the thioglycoside derivatives (14, 15) were designed, and synthesized as novel CDK2 targeting compounds.

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Cyclin-dependent kinase inhibition is considered a promising target for cancer treatment for its crucial role in cell cycle regulation. Pyrazolo pyrimidine derivatives were well established for their antitumor activity via CDK2 inhibition. In this research, new series of pyrazolopyrimidine derivatives ( 4–15 ) was designed and synthesised as novel CDK2 inhibitors. The anti-proliferative activities against MCF-7, HCT-116, and HepG-2 were used to evaluate their anticancer activity as novel CDK2 inhibitors. Most of the compounds showed superior cytotoxic activity against MCF-7 and HCT-116 compared to Sorafenib. Only compounds 8 , 14 , and 15 showed potent activity against HepG-2. The CDK2/cyclin A2 enzyme inhibitory activity was tested for all synthesised compounds. Compound 15 showed the most significant inhibitory activity with IC 50 0.061 ± 0.003 µM. It exerted remarkable alteration in Pre G1 and S phase cell cycle progression and caused apoptosis in HCT cells. In addition, the normal cell line cytotoxicity for compound 15 was assigned revealing low cytotoxic results in normal cells rather than cancer cells. Molecular docking was achieved on the designed compounds and confirmed the two essential hydrogen binding with Leu83 in CDK2 active site. In silico ADMET studies and drug-likeness showed proper pharmacokinetic properties which helped in structure requirements prediction for the observed antitumor activity.

An intravenous glucose tolerance test was carried out in i i patients with chronic manganese poisoning. Prolonged reactionary hypoglycaemia was observed. The underlying mechanism is discussed. It may be due to a disturbance of the hypothalamo-pituitary-adrenal axis.In seven of these patients total serum proteins were estimated and were separated electrophoretically. The albumin: globulin ratios were lower in patients than in controls. There were significant reductions in serum albumin concentrations and increases in concentrations of cxl and ,B globulins.Since the early discovery of chronic manganese poisoning among workers manufacturing chlorine gas in France using manganese ore (Couper, I837), many other reports from Europe, North Africa,

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