Synthesis and evaluation of anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities of some 3H-quinazolin-4-one derivatives

Nahed N E El-Sayed; Norah M Almaneai; Abir Ben Bacha; Omar Al-Obeed; Rehan Ahmad; Maha Abdulla; Ahmed M Alafeefy

doi:10.1080/14756366.2019.1574780

Synthesis and evaluation of anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities of some 3H-quinazolin-4-one derivatives

J Enzyme Inhib Med Chem. 2019 Dec;34(1):672-683. doi: 10.1080/14756366.2019.1574780.

Authors

Nahed N E El-Sayed^{1

2}, Norah M Almaneai¹, Abir Ben Bacha³, Omar Al-Obeed⁴, Rehan Ahmad⁴, Maha Abdulla⁴, Ahmed M Alafeefy⁵

Affiliations

¹ a Department of Chemistry, College of Science , King Saud University , Riyadh , Saudi Arabia.
² b National Organization for Drug Control and Research , Giza , Egypt.
³ c Biochemistry Department, College of Sciences , King Saud University , Riyadh , Saudi Arabia.
⁴ d Department of Surgery, College of Medicine , King Saud University , Riyadh , Saudi Arabia.
⁵ e Department of Chemistry , Kulliyyah of Science, International Islamic University Malaysia , Kuantan , Pahang Darul Makmur, Malaysia.

Abstract

Some new 3H-quinazolin-4-one derivatives were synthesised and screened for anticancer, antiphospholipases, antiproteases, and antimetabolic syndrome activities. Compound 15d was more potent in reducing the cell viabilities of HT-29 and SW620 cells lines to 38%, 36.7%, compared to 5-FU which demonstrated cell viabilities of 65.9 and 42.7% respectively. The IC₅₀ values of 15d were ∼20 µg/ml. Assessment of apoptotic activity revealed that 15d decreased the cell viability by down regulating Bcl2 and BclxL. Moreover, compounds, 8j, 8d/15a/15e, 5b, and 8f displayed lowered IC₅₀ values than oleanolic acid against proinflammatory isoforms of hGV, hG-X, NmPLA_2, and AmPLA₂. In addition, 8d, 8h, 8j, 15a, 15b, 15e, and 15f showed better anti-α-amylase than quercetin, whereas 8g, 8h, and 8i showed higher anti-α-glucosidase activity than allopurinol. Thus, these compounds can be considered as potential antidiabetic agents. Finally, none of the compounds showed higher antiproteases or xanthine oxidase activities than the used reference drugs.

Keywords: -quinazolin-4-one; colorectal cancer; metabolic syndrome; phospholipases; proteases.

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Proliferation / drug effects
Cell Survival / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Enzyme Inhibitors / chemical synthesis
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
HT29 Cells
Humans
Metabolic Syndrome / drug therapy*
Metabolic Syndrome / metabolism
Molecular Structure
Peptide Hydrolases / metabolism*
Phospholipases / antagonists & inhibitors*
Phospholipases / metabolism
Quinazolinones / chemical synthesis
Quinazolinones / chemistry
Quinazolinones / pharmacology*
Structure-Activity Relationship
Tumor Cells, Cultured

Substances

Antineoplastic Agents
Enzyme Inhibitors
Quinazolinones
Phospholipases
Peptide Hydrolases

Grants and funding

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding this work through research group number [RG-1435–083].