title: Synthesis and evaluation of 3-(benzylthio)-5-(1H-indol-3-yl)-1,2,4-triazol-4-amines as Bcl-2 inhibitory anticancer agents.
abstract: A series of substituted 3-(benzylthio)-5-(1H-indol-3-yl)-4H-1,2,4-triazol-4-amines has been synthesised and tested in vitro as potential pro-apoptotic Bcl-2-inhibitory anticancer agents. Synthesis of the target compounds was readily accomplished in good yields through a cyclisation reaction between indole-3-carboxylic acid hydrazide and carbon disulfide under basic conditions, followed by S-benzylation. Active compounds, such as the nitrobenzyl analogue 6c, were found to exhibit sub-micromolar IC50 values in Bcl-2 expressing human cancer cell lines. Molecular modelling and ELISA studies further implicated anti-apoptotic Bcl-2 as a candidate molecular target underpinning anticancer activity.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB Wales, UK.
authors.forename: Rania
authors.initials: R
authors.lastname: Hamdy
authors.forename: Noha
authors.initials: N
authors.lastname: Ziedan
authors.forename: Samia
authors.initials: S
authors.lastname: Ali
authors.forename: Mohamed
authors.initials: M
authors.lastname: El-Sadek
authors.forename: Elsaid
authors.initials: E
authors.lastname: Lashin
authors.forename: Andrea
authors.initials: A
authors.lastname: Brancale
authors.forename: Arwyn T
authors.initials: AT
authors.lastname: Jones
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Westwell
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014230:Triazoles