title: Synthesis, antitumor activity and molecular docking study of some novel 3-benzyl-4(3H)quinazolinone analogues.
abstract: A novel series of 3-benzyl-substituted-4(3H)-quinazolinones were designed, synthesized and evaluated for their in vitro antitumor activity. The results of this study demonstrated that 2-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide, 2-(3-benzyl-6,7-dimethoxy-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)acetamide and 3-(3-benzyl-6-methyl-4-oxo-3,4-dihydroquinazolin-2-ylthio)-N-(3,4,5-trimethoxyphenyl)-propanamide have shown amazing broad spectrum antitumor activity with mean GI(50) (10.47, 7.24 and 14.12 µM. respectively), and are nearly 1.5-3.0-fold more potent compared with the positive control 5-FU with mean GI50, 22.60 µM. On the other hand, compounds 6 and 10 yielded selective activities toward CNS, renal and breast cancer cell lines, whereas compound 9 showed selective activities towards leukemia cell lines. Molecular docking methodology was performed for compounds 7 and 8 into ATP binding site of EGFR-TK which showed similar binding mode to erlotinib, while compound 11 into ATP binding site of B-RAF kinase inhibited the growth of melanoma cell lines through inhibition of B-RAF kinase, similar to PLX4032.
authors: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors: Ibrahim A
authors: IA
authors: Al-Suwaidan
authors: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .|b Department of Medicinal Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura , Egypt .
authors: Alaa A-M
authors: AA
authors: Abdel-Aziz
authors: c Department of Pharmaceutical Chemistry , and.
authors: Taghreed Z
authors: TZ
authors: Shawer
authors: c Department of Pharmaceutical Chemistry , and.
authors: Rezk R
authors: RR
authors: Ayyad
authors: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .
authors: Amer M
authors: AM
authors: Alanazi
authors: d Department of Organic Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt .
authors: Ahmad M
authors: AM
authors: El-Morsy
authors: d Department of Organic Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt .|e Department of Pharmaceutical Chemistry , College of Pharmacy, Salman Bin Abdulaziz University , AlKharj , Saudi Arabia , and.
authors: Menshawy A
authors: MA
authors: Mohamed
authors: b Department of Medicinal Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura , Egypt .
authors: Naglaa I
authors: NI
authors: Abdel-Aziz
authors: f Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy , University of Mansoura , Mansoura , Egypt.
authors: Magda A-A
authors: MA
authors: El-Sayed
authors: a Department of Pharmaceutical Chemistry , College of Pharmacy, King Saud University , Riyadh , Saudi Arabia .|d Department of Organic Chemistry, Faculty of Pharmacy , Al-Azhar University , Cairo , Egypt .
authors: Adel S
authors: AS
authors: El-Azab
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052999:Quinazolinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000611336:3-benzyl-4(3H)quinazolinone; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D052999:Quinazolinones; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: 5-FU; NCI; erlotinib; in vitro antitumor evaluation; molecular docking; quinazoline