Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer
Mansour, M., El-Saadi, M., Amin, N., Canzoneri, J., Keeton, A., Piazza, G., abdelrahman, H. (2020). Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer. EKB Journal Management System, 63(12), 4851-4866. doi: 10.21608/ejchem.2020.28992.2624
Mostafa Mansour; Mohammed T El-Saadi; Noha H Amin; Joshua Canzoneri; Adam Keeton; Gary Piazza; hamdy abdelrahman. "Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer". EKB Journal Management System, 63, 12, 2020, 4851-4866. doi: 10.21608/ejchem.2020.28992.2624
Mansour, M., El-Saadi, M., Amin, N., Canzoneri, J., Keeton, A., Piazza, G., abdelrahman, H. (2020). 'Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer', EKB Journal Management System, 63(12), pp. 4851-4866. doi: 10.21608/ejchem.2020.28992.2624
Mansour, M., El-Saadi, M., Amin, N., Canzoneri, J., Keeton, A., Piazza, G., abdelrahman, H. Quinazolinone-Schiff's Base hybrids as Phosphodiesterase 4B inhibitors with dual activity against COPD and Lung Cancer. EKB Journal Management System, 2020; 63(12): 4851-4866. doi: 10.21608/ejchem.2020.28992.2624

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

Egyptian Journal of Chemistry
Article 17, Volume 63, Issue 12, December 2020, Page 4851-4866  XML PDF (1.64 MB)
Document Type: Original Article
DOI: 10.21608/ejchem.2020.28992.2624
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Authors
Mostafa Mansour email orcid 1; Mohammed T El-Saadi2; Noha H Amin3; Joshua Canzoneri4; Adam Keeton4; Gary Piazza4; hamdy abdelrahman5
1Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University, Beni-Suef, Egypt
2Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt Medicinal Chemistry Department, Faculty of Pharmacy, Sinai University, Ismailia, Egypt.
3Department of Medicinal Chemistry, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt
4USA Mitchell Cancer Institute Drug Discovery Laboratory, University of South Alabama, USA.
5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Nahda University, Beni-suef, Egypt Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, 71526 Assiut, Egypt
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
Quinazolinone; Schiff's; Phosphodiesterase 4B; COPD; Lung; Colon; Cancer
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