Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolopyrimidinones Tethered with Hydrazide-Hydrazones.

Chemotherapy represents the most applied approach to cancer treatment. Owing to the frequent onset of chemoresistance and tumor relapses, there is an urgent need to discover novel and more effective anticancer drugs. In the search for therapeutic alternatives to treat the cancer disease, a series of hybrid pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered with hydrazide-hydrazones, 5a–h, was synthesized from condensation reaction of pyrazolopyrimidinone-hydrazide 4 with a series of arylaldehydes in ethanol, in acid catalysis. In vitro assessment of antiproliferative effects against MCF-7 breast cancer cells, unveiled that 5a, 5e, 5g, and 5h were the most effective compounds of the series and exerted their cytotoxic activity through apoptosis induction and G0/G1 phase cell-cycle arrest. To explore their mechanism at a molecular level, 5a, 5e, 5g, and 5h were evaluated for their binding interactions with two well-known anticancer targets, namely the epidermal growth factor receptor (EGFR) and the G-quadruplex DNA structures. Molecular docking simulations highlighted high binding affinity of 5a, 5e, 5g, and 5h towards EGFR. Circular dichroism (CD) experiments suggested 5a as a stabilizer agent of the G-quadruplex from the Kirsten ras (KRAS) oncogene promoter. In the light of these findings, we propose the pyrazolo-pyrimidinone scaffold bearing a hydrazide-hydrazone moiety as a lead skeleton for designing novel anticancer compound

Options for continuous radar Earth observations

Near Real Time (minutes or hours) radar imaging of ground targets located anywhere on an hemi- sphere, with or without interferometric coherence with previous passes, can be obtained with different solutions that are considered here. Geosynchronous systems, from the one proposed in 1978 by Tomiyasu to telecom satellite compatible solutions, and Low, Medium or Geosynchronous Earth Orbit constellations are discussed. Their benefits, problems, and sizes are briefly summarized, and a comparative table is presented. If interfer-ometric coherence is requested, continuous imaging is obtained only if a very wide geostationary aperture is progressively scanned, eventually using a MIMO (Multiple Input Multiple Output) combination of several slow librating small satellites. Instead, fast librating, strip mapping, large geosynchronous satellites do provide high resolution imaging, but interferometry (and thus coherent change detection) is achievable only after a minimum delay of 12 h, i.e., when the target comes in sight without need to squint the antenna. Hence, both complex and simple systems reach full resolution interferometric imaging and thus coherent change detection capability only after 12 h