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A series of 2,4-dichloro-5-{[4-(phenylsulfonyl)piperazin-1-yl]carbonyl}benzenesulfonamides were designed and synthesized through amidation of Lasamide 1 with substituted piperazines. The newly obtained compounds demonstrated remarkable inhibition potency and selectivity for the human (h) expressed Carbonic Anhydrase (CA; EC 4.2.1.1) II isoform. Selected compounds 7 and 9 were investigated in an in vivo model of glaucoma and showed relevant performances, with the latter being able to last the effect up to 4 hours. The results herein reported are in sustainment of Lasamide derivatives as a new class of compounds potentially exploitable for the management of uncontrolled intra ocular pressure (IOP)., (© 2024 The Authors. ChemMedChem published by Wiley-VCH GmbH.)

In this study, a focused library of oxime ester derivatives of 2,4-dichloro-5-sulfamoylbenzoic acid (lasamide) containing Schiff bases was synthesized and tested in vitro for their ability to inhibit the cytosolic human carbonic anhydrases (hCAs) I and II, as well as the transmembrane and tumor-associated IX and XII isoforms. As a result, we obtained a first line of knowledge on lasamide derivatives potentially useful for development as CA inhibitors (CAIs). In particular, we focused our attention on the derivative 11 , which was selective toward hCAs IX and XII over the cytosolic isoenzymes. An in silico study was conducted to assess the binding mode of 11 within hCAs IX and XII. Also, antiproliferative assays highlighted promising derivatives. The data obtained in this study are currently in use for the development of better-performing compounds on the tumor-associated isoforms., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Objectives: The main objective of the present investigation to develop and evaluate solid dispersions of BCS Class II drugs etoricoxib employing various natural polymers, compatible with conventional manufacturing method to enhance solubility of poorly soluble drugs., Materials and Methods: In this study, etoricoxib solid dispersion were prepared using xanthan gum, gaur gum and acacia and their combinations by solvent evaporation method. Solid dispersions and pure etoricoxib in the form of powder were characterized in comparison with pure drug and corresponding physical mixtures in the same ratios by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), powder X-ray diffractogram, and in vitro drug release., Results: Solid dispersion (ET11) prepared with 1: 2: 2: 2 drug carrier ratios were showed highest solubility in different solvents. Hence the solid dispersion (ET11) of 1: 2: 2: 2 ratios were selected for characterization. The DSC study indicated that the crystalline nature of etoricoxib was reduced to amorphous. The diffraction pattern of the solid dispersions in each figure indicates that diffraction peaks at 2ɵ values has less intensity than that of pure drugs. This indicated that the crystalline nature of drug sample was converted to amorphous with ET11. Scanning electron microscope photographs of solid dispersion seem to be more porous in nature. From the in vitro drug release profile, it can be seen that formulation ETM11 shows higher dissolution rate i.e. 98.2±1.3% compared with other formulations. It is predicted that, increasing concentration of carrier, increases the drug dissolution rate., Conclusion: This study has shown that the solid dispersion of etoricoxib using natural carrier can be promising formulation for solubility and dissolution enhancement. Natural polymers used have shown promising results in the modification of drug release from the formulations., Competing Interests: Conflicts of interest: No conflict of interest was declared by the authors., (©Copyright 2020 Turk J Pharm Sci, Published by Galenos Publishing House.)