title: Novel 9-(alkylthio)-Acenaphtho[1,2-e]-1,2,4-triazine derivatives: synthesis, cytotoxic activity and molecular docking studies on B-cell lymphoma 2 (Bcl-2).
abstract: OBJECTIVE
  Acenaphtho derivatives have been reported as antitumor agents. Due to this fact and also with the aim of developing the chemistry of potentially bioactive heterocyclic compounds via efficient reactions, a facile procedure for the synthesis of 9-(alkylthio)-acenaphtho[1,2-e]-1,2,4-triazines via two step condensation of thiosemicarbazide and acenaphtylene-9,10-quinone to form acenaphtho[1,2-e]-1,2,4-triazine-9(8H)-thiones and subsequent reaction with benzyl chloride derivatives is reported.
  
  
  METHODS
  9-(alkylthio) acenaphtho[1,2-e]-1,2,4-triazines were synthesized via the reaction of acenaphtho-9,10-quinone with thiosemicarbazide, and then with the benzyl chloride derivatives. Cytotoxicity of some prepared compounds was assessed through MTT assay on three different human cancerous cell lines (HL-60, MCF7, and MOLT-4 cells). Molecular docking studies were performed via AutoDock4.2 software in order to confirm an apoptosis-inducing activity of acenaphtho scaffolds via the Bcl-2 protein.
  
  
  RESULTS
  Excellent yields of the products, short reaction times and simple work-up are attractive features of this synthetic protocol. The evaluated compounds exhibited moderate to good cytotoxic activities. Docking results on the active site of B-cell lymphoma 2 (Bcl-2) supported the experimental biological data and agreed well with previous in silico data for commonly used anti-cancer drugs. Moreover; results were analyzed considering binding efficiency indices.
  
  
  CONCLUSIONS
  The outcomes of the present study may be helpful in future targeting of Bcl-2 with the aim of developing apoptosis-inducing agents.
authors.forename: Mohammad K
authors.initials: MK
authors.lastname: Mohammadi
authors.forename: Omidreza
authors.initials: O
authors.lastname: Firuzi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Khoshneviszadeh
authors.forename: Nima
authors.initials: N
authors.lastname: Razzaghi-Asl
authors.forename: Saghi
authors.initials: S
authors.lastname: Sepehri
authors.affiliation: Medicinal and Natural Products Chemistry Research Center, Shiraz, University of Medical Sciences, PO Box 3288-71345, Shiraz, Iran. mirir@sums.ac.ir.
authors.forename: Ramin
authors.initials: R
authors.lastname: Miri