title: DESIGN, SYNTHESIS, MOLECULAR DOCKING AND ANTI-BREAST CANCER ACTIVITY OF NOVEL QUINAZOLINONES TARGETING ESTROGEN RECEPTOR α.
abstract: A new series of 6,8-dibromo-2-(4-chlorophenyl)-4-oxo-4H-quinazoline derivatives II-VI were syn- thesized, their chemical structures were confirmed by spectroscopic means and elemental analyses. All these compounds were tested in vitro against human breast cancer cell line (MCF-7) using resazurin reduction assay method and doxorubicin as a reference drug. Most of the tested compounds showed better activity than dox- orubicin. Compound IVh was the best active one, its IC₅₀ is 8.52 µg/mL. Molecular docking studies for the best active compounds IVb, IVc, IVf, IVh and Va were performed on the active site of estrogen receptor α (ERα) subtype to explore the estrogen receptor binding ability of these compounds. All the docked compounds showed good fitting score energy with the active site of ERα subtype and compound IVh showed the best docking score energy(-25.3 kcal/mol). Estrogen binding evaluation assay was performed for the docked compounds to ensure that their activity against MCF7 go through inhibition of ERα, they showed ERα inhibition at 41-85% and compound IVh was the most active one (85%).
authors.forename: Marwa F
authors.initials: MF
authors.lastname: Ahmed
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Youns
authors.forename: Amany
authors.initials: A
authors.lastname: Belal
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D052999:Quinazolinones