مشتقات جدید 9-(آلکیل تیو)-اسنفتو تری آزین: سنتز، خاصیت سیتوتوکسیک و داکینگ مولکولی

عنوان انگليسی

Novel 9-(alkylthio)-Acenaphtho[1,2-e]-1,2,4-triazine derivatives: synthesis, cytotoxic activity and molecular docking studies

خلاصه انگلیسی

BACKGROUND AND PURPOSE OF THE STUDY: 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.

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