title: Synthesis, cytotoxic evaluation and molecular docking study of novel quinazoline derivatives as PARP-1 inhibitors.
abstract: Novel series of spiro[(2H,3H)-quinazoline-2,1'-cyclohexane] derivatives (I-XVI) were synthesized and biologically evaluated as cytotoxic agents against human breast carcinoma cell lines (MCF-7) using doxorubicin as a reference drug. Most of the tested compounds displayed promising cytotoxic activity, especially derivatives V, VIb and XIb. The most active compounds were docked into the PARP-1 enzyme binding site to predict the ligand-protein binding modes. Lipinski rule of five and ADME profile suggested strongly that compounds V and VIb are promising agents as breast cancer inhibitors with drug likeness approach that have PARP-1 inhibitory activity. The structures of all newly synthesized compounds were confirmed by microanalysis and IR, 1H-NMR and mass spectral data.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Egypt.
authors.forename: Kamelia M
authors.initials: KM
authors.lastname: Amin
authors.forename: Manal M
authors.initials: MM
authors.lastname: Anwar
authors.forename: Mohsen M
authors.initials: MM
authors.lastname: Kamel
authors.forename: Emad M M
authors.initials: EM
authors.lastname: Kassem
authors.forename: Yasmin M
authors.initials: YM
authors.lastname: Syam
authors.forename: Samia A
authors.initials: SA
authors.lastname: Elseginy
mesh_terms: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011799:Quinazolines; D004317:Doxorubicin; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases