title: Virtual screening, SAR, and discovery of 5-(indole-3-yl)-2-[(2-nitrophenyl)amino] [1,3,4]-oxadiazole as a novel Bcl-2 inhibitor.
abstract: A new series of oxadiazoles were designed to act as inhibitors of the anti-apoptotic Bcl-2 protein. Virtual screening led to the discovery of new hits that interact with Bcl-2 at the BH3 binding pocket. Further study of the structure-activity relationship of the most active compound of the first series, compound 1, led to the discovery of a novel oxadiazole analogue, compound 16j, that was a more potent small-molecule inhibitor of Bcl-2. 16j had good in vitro inhibitory activity with submicromolar IC50values in a metastatic human breast cancer cell line (MDA-MB-231) and a human cervical cancer cell line (HeLa). The antitumour effect of 16j is concomitant with its ability to bind to Bcl-2 protein as shown by an enzyme-linked immunosorbent assay (IC50= 4.27 μm). Compound 16j has a great potential to develop into highly active anticancer agent.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.|Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Noha I
authors.identifier: 0000-0002-9522-2188
authors.initials: NI
authors.lastname: Ziedan
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.|Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
authors.forename: Rania
authors.initials: R
authors.lastname: Hamdy
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cavaliere
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.|Cardiff China Medical Research Collaborative, Cardiff University, Cardiff, UK.
authors.forename: Malamati
authors.initials: M
authors.lastname: Kourti
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors.forename: Filippo
authors.initials: F
authors.lastname: Prencipe
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors.forename: Arwyn T
authors.initials: AT
authors.lastname: Jones
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UK.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000737:chemistry; D062105:Molecular Docking Simulation; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C000622442:5-(1H-indol-3-yl)-N-(2-nitrophenyl)-1,3,4-oxadiazole-2-amine; D000970:Antineoplastic Agents; D007211:Indoles; D010069:Oxadiazoles; D019253:Proto-Oncogene Proteins c-bcl-2; C030374:indole
keywords: 
  SAR
  ; BCl-2 inhibitor; anti-cancer; drug design; virtual screening