Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer

Mansour, Mostafa; El-Saadi, Mohammed T; Amin, Noha H; Canzoneri, Joshua; Keeton, Adam; Piazza, Gary; Abdelrahman, Hamdy

doi:10.21608/ejchem.2020.28992.2624

Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer

Document Type : Original Article

Authors

¹ Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt

² Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University, Ismailia, Egypt.

³ Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt

⁴ USA Mitchell Cancer Institute Drug Discovery Laboratory, University of South Alabama, USA.

⁵ Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, Beni-suef, Egypt Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt

10.21608/ejchem.2020.28992.2624

Abstract

A series of thirty compounds of quinazolinone-Schiff's base hybrids were rationally designed, synthesized, and evaluated for their in vitro Phosphodiesterase 4B inhibition, anti-lung and anti-colon cancer activities. Compounds 9, 16, 23, 29, 30, 31, 32 and 33, each possessing a tri-hydroxy moiety, showed the highest inhibitory activity (56.05-89.07%) at 10 µM concentration if compared to rolipram. Compounds 16 and 23 showed good anti-lung cancer activity with IC50 1.55 and 1.30 µM, respectively. Moreover, compound 16 showed high anti-colon cancer activity with IC50 0.6 µM. Compound 33 showed good affinity and molecular binding modes towards the key amino acid Gln 443 and Phe 446 for inhibition of the target enzyme. Finally, active compounds showed good ADME calculations.

Keywords