Ultrasound One Pot Synthesis of Fused Quinazolinones and Quinazolinediones, Screening and Molecular Docking Study as Phosphodiesterase 7A Inhibitors

Elfeky, Sherin; Sobahi, Tariq; Gineinah, Magdy M; Ahmed, Nesreen S

doi:10.21608/ejchem.2019.7130.1587

Ultrasound One Pot Synthesis of Fused Quinazolinones and Quinazolinediones, Screening and Molecular Docking Study as Phosphodiesterase 7A Inhibitors

Document Type : Original Article

Authors

¹ Department of Pharmaceutical organic chemistry, Faculty of Pharmacy, Mansoura University,Egypy

² king abdulaziz university, Jeddah, faculty of science

³ king abdulaziz university, Jeddah, faculty of Pharmacy

⁴ Department of Medicinal Chemistry, National Research Center, Cairo, Egypt

10.21608/ejchem.2019.7130.1587

Abstract

Phosphodiesterase 7A enzyme is one the most recent targets for designing potent anti-inflammatory agents with minimal side effects. Quinazolinones are unique building blocks of wide biological activities. Different Quinazolinones were reported to act as Phosphodiesterase 7A inhibitors anti-inflammatory particularly against choronic inflammation and autoimmune disease. Ultrasound is a green convenient method for synthesis of different heterocyclic ring system that is advantageous in terms of yield and reaction time. Ultrasound was used for one pot synthesis of 3-substituted 6-aryl-dihydroisoindolo[2,1-a]quinazoline-5,11-diones and 3-Aryl quinazoline-2,4(1H,3H)-diones. Seventeen compounds were synthesized in good yields. The synthesized compounds were inspected for in vitro inhibitory activity against phosphodiesterase7A enzyme. Molecular docking was used to study the mode of interaction of all the synthesized compounds into the enzyme phosphodiesterase 7A binding site. Five compounds showed high inhibitory activity of enzyme Phosphodiesterase 7A at micro-molar level compared to reference drug. The compounds showed good recognition at the enzyme binding site in the molecular docking. There was a good agreement between the molecular docking and the biological screening results.

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