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51.
Steven Elder John Graham Roberson James Warren Robert Lawson Daniel Young Sean Stokes Matthew K. Ross 《Molecules (Basel, Switzerland)》2022,27(12)
In this study, kartogenin was incorporated into an electrospun blend of polycaprolactone and poly(lactic-co-glycolic acid) (1:1) to determine the feasibility of this system for sustained drug delivery. Kartogenin is a small-molecule drug that could enhance the outcome of microfracture, a cartilage restoration procedure, by selectively stimulating chondrogenic differentiation of endogenous bone marrow mesenchymal stem cells. Experimental results showed that kartogenin did not affect the electrospinnability of the polymer blend, and it had negligible effects on fiber morphology and scaffold mechanical properties. The loading efficiency of kartogenin into electrospun membranes was nearly 100%, and no evidence of chemical reaction between kartogenin and the polymers was detected by Fourier transform infrared spectroscopy. Analysis of the released drug using high-performance liquid chromatography–photodiode array detection indicated an abundance of kartogenin and only a small amount of its major hydrolysis product. Kartogenin displayed a typical biphasic release profile, with approximately 30% being released within 24 h followed by a much slower, constant rate of release up to 28 days. Although additional development is needed to tune the release kinetics and address issues common to electrospun scaffolds (e.g., high fiber density), the results of this study demonstrated that a scaffold electrospun from biodegradable synthetic polymers is a suitable kartogenin delivery vehicle. 相似文献
52.
Christine N. Morrison Kathleen E. Prosser Ryjul W. Stokes Anna Cordes Nils Metzler-Nolte Seth M. Cohen 《Chemical science》2022,13(32):9450
Correction for ‘Expanding medicinal chemistry into 3D space: metallofragments as 3D scaffolds for fragment-based drug discovery’ by Christine N. Morrison et al., Chem. Sci., 2020, 11, 1216–1225, https://doi.org/10.1039/C9SC05586J.The authors regret that in the original article, inhibitory values reported for some metallofragments were incorrect. Unfortunately, DMSO stock solutions of reportedly active ferrocene-based metallofragments were found to decompose in the presence of light, which resulted in inaccurate inhibition values. The authors maintain that the core conclusions of the paper are accurate and the utility of three-dimensional metal complexes for fragment-based drug discovery has merit.In the original article, ‘class A’ metallofragments are comprised of ferrocene derivatives (Fig. 1). Some of these ferrocene fragments (specifically those containing carbonyl groups) are reported as broadly inhibiting several protein targets. It was noted in our original report that the ferrocene scaffold was likely promiscuous due to its lipophilicity and potential redox activity, but that it might still serve as a useful metallofragment for fragment-based drug discovery (FBDD) campaigns. However, re-evaluation of these compounds against the influenza endonuclease (PAN) failed to reproduce our original inhibition results for the class A metallofragments using freshly prepared stocks, indicating a problem with the materials used in the original study.Open in a separate windowFig. 1Chemical structures of class A metallofragments.Several compounds from class A were originally reported as having near complete (100%) inhibition against PAN endonuclease at an inhibitor concentration of 200 μM (and2).2). However, when re-evaluated under identical conditions, using freshly prepared DMSO stock solutions, inhibition was only observed with one fragment of this class (A22, Fig. 1), with the previously reported highly active fragments (A4, A7–A21, Compound A1 A2 A3 A4 A5 A7 A8 A9 A10 A11 Reported 12 ± 6 <1 <1 45 ± 14 8 ± 7 103 ± 5 103 ± 4 53 ± 5 46 ± 7 90 ± 5 Corrected 3 ± 10 n.d. 18 ± 3 6 ± 3 21 ± 5 9 ± 3 10 ± 5 4 ± 2 16 ± 4 10 ± 7