BIOMAT Database Logo BIOMAT Database Logo

Synthesis and evaluation of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines as Bcl-2 inhibitory anticancer agents. 2017

Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, Wales, UK; Faculty of Pharmacy, Zagazig University, Egypt.

A series of 5-(1H-indol-3-yl)-N-aryl-1,3,4-oxadiazol-2-amines 8a-j has been designed, synthesized and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents based on our previous lead compound 8a. Synthesis of the target compounds was readily accomplished through a cyclisation reaction between indole-3-carboxylic acid hydrazide (5) and substituted isothiocyanates 6a-j, followed by oxidative cyclodesulfurization of the corresponding thiosemicarbazide 7a-j using 1,3-dibromo-5,5-dimethylhydantoin. Active compounds of the series 8a-j were found to have sub-micromolar IC50 values selectively in Bcl-2 expressing human cancer cell lines; notably the 2-nitrophenyl analogue 8a was found to exhibit potent activity, and compounds 8a and 8e possessed comparable Bcl-2 binding affinity (ELISA assay) to the established natural product-based Bcl-2 inhibitor, gossypol. Molecular modeling studies helped to further rationalise anti-apoptotic Bcl-2 binding, and identified compounds 8a and 8e as candidates for further development as Bcl-2 inhibitory anticancer agents.

UI MeSH Term Description Entries
D010069 Oxadiazoles Compounds containing five-membered heteroaromatic rings containing two carbons, two nitrogens, and one oxygen atom which exist in various regioisomeric forms. Oxadiazole
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000970 Antineoplastic Agents Substances that inhibit or prevent the proliferation of NEOPLASMS. Anticancer Agent,Antineoplastic,Antineoplastic Agent,Antineoplastic Drug,Antitumor Agent,Antitumor Drug,Cancer Chemotherapy Agent,Cancer Chemotherapy Drug,Anticancer Agents,Antineoplastic Drugs,Antineoplastics,Antitumor Agents,Antitumor Drugs,Cancer Chemotherapy Agents,Cancer Chemotherapy Drugs,Chemotherapeutic Anticancer Agents,Chemotherapeutic Anticancer Drug,Agent, Anticancer,Agent, Antineoplastic,Agent, Antitumor,Agent, Cancer Chemotherapy,Agents, Anticancer,Agents, Antineoplastic,Agents, Antitumor,Agents, Cancer Chemotherapy,Agents, Chemotherapeutic Anticancer,Chemotherapy Agent, Cancer,Chemotherapy Agents, Cancer,Chemotherapy Drug, Cancer,Chemotherapy Drugs, Cancer,Drug, Antineoplastic,Drug, Antitumor,Drug, Cancer Chemotherapy,Drug, Chemotherapeutic Anticancer,Drugs, Antineoplastic,Drugs, Antitumor,Drugs, Cancer Chemotherapy
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D019253 Proto-Oncogene Proteins c-bcl-2 Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma. bcl-2 Proto-Oncogene Proteins,c-bcl-2 Proteins,B-Cell Leukemia 2 Family Proteins,BCL2 Family Proteins,BCL2 Proteins,B Cell Leukemia 2 Family Proteins,Family Proteins, BCL2,Proteins, BCL2,Proteins, BCL2 Family,Proto Oncogene Proteins c bcl 2,Proto-Oncogene Proteins, bcl-2,bcl 2 Proto Oncogene Proteins,c bcl 2 Proteins,c-bcl-2, Proto-Oncogene Proteins

Related Publications

Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Synthesis of new S-substituted derivatives of 5-[3-(1H-indol-3-yl)propyl]-1,3,4-oxadiazol-2-ylhydrosulfide as suitable antibacterial and anticancer agents with moderate cytotoxicity.
November 2019, Pakistan journal of pharmaceutical sciences,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Synthesis and anticancer activity of N-aryl-5-substituted-1,3,4-oxadiazol-2-amine analogues.
January 2014, BioMed research international,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Synthesis, molecular modeling and biological evaluation of N-benzylidene-2-((5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl)thio)acetohydrazide derivatives as potential anticancer agents.
January 2014, Bioorganic & medicinal chemistry,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Discovery of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines as potent PIM inhibitors.
February 2015, Bioorganic & medicinal chemistry letters,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
[Synthesis and antibacterial activity of 2-(3-pyridyl)-5-([(5-aryl-1,3,4-oxadiazol-2-yl) methylene]thio)-1,3,4-oxadiazoles].
April 2004, Yao xue xue bao = Acta pharmaceutica Sinica,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
One-pot, four-component synthesis of novel cytotoxic agents 1-(5-aryl-1,3,4-oxadiazol-2-yl)-1-(1H-pyrrol-2-yl)methanamines.
May 2014, European journal of medicinal chemistry,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Synthesis and antifungal activity of 3-(1,3,4-oxadiazol-5-yl)-indoles and 3-(1,3,4-oxadiazol-5-yl)methyl-indoles.
May 2013, European journal of medicinal chemistry,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Discovery and SAR exploration of N-aryl-N-(3-aryl-1,2,4-oxadiazol-5-yl)amines as potential therapeutic agents for prostate cancer.
March 2010, Chemistry Central journal,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Polymorphism of 3-(5-phenyl-1,3,4-oxadiazol-2-yl)- and 3-[5-(pyridin-4-yl)-1,3,4-oxadiazol-2-yl]-2H-chromen-2-ones.
November 2019, Acta crystallographica. Section C, Structural chemistry,
Rania Hamdy, and Noha I Ziedan, and Samia Ali, and Cinzia Bordoni, and Mohamed El-Sadek, and Elsaid Lashin, and Andrea Brancale, and Arwyn T Jones, and Andrew D Westwell
Synthesis and biological screening of 5-(alkyl(1H-indol-3-yl))-2-(substituted)-1,3,4-oxadiazoles as antiproliferative and anti-inflammatory agents.
August 2013, European journal of medicinal chemistry,
Copied contents to your clipboard!