Celastrol strongly binds to AMPK activating site: A docking study

The AMP-activated protein kinase (AMPK) is a central regulator of cellular metabolism andenergy homeostasis in mammalian tissues. According to key role of AMPK in controlling energyhomeostasis, its activation can be related with metabolic disease, including type ۲ diabetes and cancertreatment. Therefore, AMPK activators can be potential anti-cancer agents “[۱]”. The aim of this studyis evaluation of Berberine, Caffeic acid, Celastrol, Curcumin (Cum), Luteolin, Metformin“[۲]”,Salicylat, Staurosporine (Stu)“[۳]”, R۳۴ and ۶VT on AMPK by molecular docking. Three-dimensional(۳D) structure of the compounds “[۴]” and AMPK (two states, ۶C۹F and ۵KQ۵) were obtained fromthe PubChem database and Protein Data Bank (PDB) respectively. Finally, the molecular docking wasstudied using Autodock ۴.۱ software. Analyses of molecular docking exhibited that STU ligand ispresent in both active sites of ۶C۹F and ۵KQ۵ proteins with highest binding free energy with -۱۱.۶۸kcal/mol in ۶C۹F and -۱۳.۳۴ kcal/mol in ۵KQ۵ compared to the other compounds. After the STU,Celastrol displayed the highest binding energy with -۱۰.۴۴ kcal/mol and Metformin showed the lowestbinding energy with -۳.۰۳ kcal/mol. According to the obtained results, it was suggested that among thecompounds (except for STU) Celastrol may have had activating effect on AMPK. Therefore, AMPKcan be a potential target to celastrol in cancer treatment.

کلیدواژه ها:

AMPK ، Cancer treatment ، Celastrol ، Molecular docking