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401.
Anca-Roxana Petrovici Mihaela Silion Natalia Simionescu Rami Kallala Mariana Pinteala Stelian S. Maier 《International journal of molecular sciences》2022,23(11)
Zoledronic acid (ZA) is used in the treatment of various bone pathologies, but it forms complexes with calcium ions present in body fluids, decreasing ZA bioavailability. Thereby, the study first describes the identification of ZA-calcium complexes that form in calcium-rich environments, in order to establish the bioavailable ZA concentration. Then, a new method for quantification of low ZA amounts in milieus that mimics in vivo conditions by using simulated body fluid and calcium sulfate hemihydrate was described. Almost all analytical methods of ZA quantification described in the literature require compound derivatization. At very low concentrations, derivatization is prone to analyte loss, therefore compromising the analytical results. In our study, we avoided ZA derivatization by using a high-performance liquid chromatography and electrospray ionization mass spectrometry (HPLC-ESI-MS) system, conducting the investigation based on the fragmentation mass extracted ion chromatograms specific to the ZA protonated form. The method was validated by selectivity, precision, accuracy, linearity, signal to noise ratio, and limit of detection and limit of quantification calculation. Experimentally, this method can detect ranges of 0.1–0.5 ng/mL and precisely quantify ZA concentrations as low as 0.1 ng/mL. This method could provide the basis for quantifying low amounts of ZA in the blood during long-term administration. 相似文献
402.
In this paper, we propose a parallel algorithm to solve the convex hull problem for an (n×n) multi-leveled image using a reconfigurable mesh connected computer of the same size as a computational model. The algorithm determines parallely the convex hull of all the connected components of the multileveled image. It is based on some geometric properties and a top-down strategy. The complexity of the algorithm is O(logn) times. Using some approximations on the component contours, this complexity is reduced to O(logm) times where m is the number of the vertices of the convex hull of the biggest component of the image.This complexity is reached thanks to the polymorphic properties of the mesh where all the components are simultaneously and separately processed. 相似文献
403.
Dr. Mohamed Ettaoussi Amélie Laversin Brandon Vreulz Dr. Marouane Rami Dr. Nicolas Lebegue Dr. Philippe Delagrange Dr. Daniel Henri Caignard Prof. Patricia Melnyk Dr. Maxime Liberelle Dr. Saïd Yous 《ChemMedChem》2022,17(3):e202100658
In our constant search for new successors of agomelatine, we report herein a new series of compounds resulting from bioisosteric modulation of the naphthalene ring. The isoquinoline and tetrahydroisoquinoline derivatives were synthesized and pharmacologically evaluated. This isosteric replacement of the naphthalene group of agomelatine has led to potent agonist and partial agonist compounds with nanomolar melatonergic binding affinities. Overall, the presence of a nitrogen atom was accompanied with a decrease in the binding affinity toward both MT1 and MT2 and the loss of 5HT2C response, especially for tetrahydroisoquinoline in comparison with the parent compound. Interestingly, due to the presence of this nitrogen atom, a notable improvement in the pharmacokinetic properties was observed for all compounds. 相似文献