Identifying Phosphodiesterase‐5 Inhibitors with Drug Repurposing Approach: Implications in Vasodysfunctional Disorders

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Identifying Phosphodiesterase-5 Inhibitors with Drug Repurposing Approach: Implications in Vasodysfunctional Disorders

Phosphodiesterase type 5 plays a crucial role in regulating key signaling molecules involved in various physiological processes. This study combines virtual screening and molecular dynamics simulations to investigate the repurposing of FDA-approved drugs as potential PDE5 inhibitors.


Abstract

Phosphodiesterase type 5 (PDE5) is a multidomain protein that plays a crucial role in regulating cellular cyclic guanosine monophosphate (cGMP), a key signaling molecule involved in various physiological processes. Dysregulation of PDE5 and cGMP signaling is associated with a range of vasodysfunctional disorders, necessitating the development of effective therapeutic interventions. This study adopts comprehensive approach, combining virtual screening and molecular dynamics (MD) simulations, to repurpose FDA-approved drugs as potential PDE5 inhibitors. The initial focus involves selecting compounds based on their binding affinity. Shortlisted compounds undergo a meticulous analysis for their drug profiling and biological significance, followed by the activity evaluation and interaction analysis. Notably, based on binding potential and drug profiling, two molecules, Dutasteride and Spironolactone, demonstrate strong potential as PDE5 inhibitors. Furthermore, all atom MD simulations were employed (500 ns) to explore dynamic behavior of Dutasteride and Spironolactone in complexes with PDE5. Principal components analysis (PCA) and free energy landscape (FEL) analyses are further leveraged to decipher that the binding of Dutasteride and Spironolactone stabilizes the structure of PDE5 with minimal conformational changes. In summary, Dutasteride and Spironolactone exhibit remarkable affinity for PDE5 and possess characteristics that suggest their potential as therapeutic agents for conditions associated with PDE5 dysfunction.

Surface Modification of Lignite with Alkyl and Mixed Alkyl‐Aryl Films Generated from an Aryl Diazonium Salt and Alkyl Halides: Experimental Results and Theoretical Analyses

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Surface Modification of Lignite with Alkyl and Mixed Alkyl-Aryl Films Generated from an Aryl Diazonium Salt and Alkyl Halides: Experimental Results and Theoretical Analyses

The surface of lignite has been modified with alkylcarboxylic moieties derived from alkyl halides by diverting the reactivity of the sterically hindered aryl radical obtained by reduction of the 2,6-dimethylbenzene diazonium tetrafluoroborate after its chemical reduction. Mixed alkyl-aryl layers are prepared by using 4-nitro or 3,5-bis-trifluoro benzenediazonium salts.


Abstract

In search of new possible uses of cheap lignite from the Kosova Bassin, the surface of lignite powders is modified with alkyl or mixed alkyl-aryl layers. Modification is performed in aqueous acid solution containing an aryl diazonium salt and an alkyl halide compound in millimolar concentration, in the presence of potassium iodide as a reducing agent at equimolar concentration. Attachment of alkyl films substituted with carboxylic groups and aryl films with nitro or bis-trifluoromethyl groups is characterized by IRATR and XPS spectroscopy. The formation of a stable interface during the grafting reactions of alkyl and aryl moieties with lignite surface has been confirmed by theoretical calculations. Aryl diazonium salts once chemically or spontaneously reduced are a source of aryl radicals, able to attach chemically to the material surface or to react with alkyl halides by abstracting the halogen atom. If the aryl diazonium salts are unable to graft to the coal surface due to steric hindrance, they can, nevertheless, abstract an iodine or bromine atom to generate alkyl radicals that react with the material surface.

Quasicrystalline Antimony Thin Films

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Quasicrystalline Antimony Thin Films


Abstract

The growth of antimony (Sb) thin films on the fivefold surface of icosahedral Ag−In−Yb quasicrystal has been studied by scanning tunneling microscopy (STM) and x-ray photoelectron spectroscopy (XPS). At low coverage, the deposited Sb yields a network of pentagons of different sizes and heights. These Sb pentagons can be mapped by a pentagonal tiling of the substrate and thus exhibit quasicrystalline long-range order. Subsequent deposition of Sb yields a disordered film. XPS observations of the growth mode are consistent with the STM results.