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Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors

Abdel Haleem M. Hussein, Ahmed A. Khames, Abu‐Bakr A. A. M. El‐Adasy, Ahmed A. Atalla, Mohamed Abdelrady, Mohamed I. A. Hassan, Mohamed T. M. Nemr, Yaseen A. M. M. Elshaier

2020RSC Advances49 citationsDOIOpen Access PDF

Abstract

= 0.09-0.71 μM range). Moreover, a molecular docking study was implemented to reveal the binding interactions of potent compounds in the binding sites of PDE5 (PDB ID 2H42), COX-1 and COX-2 (PDB ID 3LN1) enzymes. For the interaction with the PDE5 enzyme, activator compounds had a strong binding mode (HB with Gln817:A) than inhibitory derivatives. Both types of compounds are considered as PDE5 regulators. This novel finding will encourage us to discover a new pharmacological application of small chemical entities as the PDE5 enhancer, or will lower side effects as PDE5 inhibitors. All active compounds adopted the Y-shape along the COX-2 active site.

Topics & Concepts

ChemistrycGMP-specific phosphodiesterase type 5Protein Data Bank (RCSB PDB)PharmacologyIC50EnzymeActive siteDocking (animal)Inhibitory postsynaptic potentialPhosphodiesteraseStructure–activity relationshipBiological activityStereochemistrySildenafilBiochemistryIn vitroBiologyMedicineInternal medicineNursingPhosphodiesterase function and regulationPhenothiazines and Benzothiazines Synthesis and ActivitiesSynthesis and Catalytic Reactions
Design, synthesis and biological evaluation of new 2-aminothiazole scaffolds as phosphodiesterase type 5 regulators and COX-1/COX-2 inhibitors | Litcius