Lateef Mehreen, Azhar Abid, Siddiqui Bina S, Zarina Shamshad, Uddin Nizam, Anwar Muhammad F, Siddiqui Kauser, Azhar Kaniz F, Iqbal Lubna, Mehmood Rashad, Perveen Shagufta
Pakistan Council of Scientific and Industrial Research Laboratories Complex, Karachi-75280, Pakistan.
The Karachi Institute of Biotechnology and Genetic Engineering, University of Karachi, Karachi-75270, Pakistan.
Heliyon. 2017 Jul 10;3(7):e00350. doi: 10.1016/j.heliyon.2017.e00350. eCollection 2017 Jul.
To treat Alzheimer's disease (AD), the available candidates are effective only against mild AD or have side effects. So, a study was planned to synthesis new candidates that may have good potential to treat AD. A series of new anthrarobin acyl derivatives (-) were synthesized by the reaction of anthrarobin () and acetic anhydride/acyl chlorides. The product were characterized by H NMR and EI-MS, and evaluated for butyrylcholinesterase (BuChE) inhibition activity. Compounds and showed notable BuChE inhibitory potential with IC 5.3 ± 1.23 and 17.2 ± 0.47 μM, respectively when compared with the standard eserine (IC 7.8 ± 0.27 μM), compound showed potent BuChE inhibition potential than the standard eserine. The active compounds and have acyl groups at 2-OH and 10-OH positions which may be responsible for inhibitory potential as this orientation is absent in other products. studies of and products revealed the high inhibitory potential due to stable binding of ligand with the BuChE active sites with docking energy score -18.8779 kcal/mol and -23.1159 kcal/mol, respectively. Subsequently, compound that have potent BuChE inhibitory activity could be the potential candidate for drug development for Alzheimer's disease.
为了治疗阿尔茨海默病（AD），现有的候选药物仅对轻度AD有效或具有副作用。因此，计划开展一项研究来合成可能具有良好AD治疗潜力的新候选药物。通过蒽喏宾（）与乙酸酐/酰氯反应合成了一系列新的蒽喏宾酰基衍生物（-）。产物通过1H NMR和EI-MS进行表征，并评估其对丁酰胆碱酯酶（BuChE）的抑制活性。与标准药物毒扁豆碱（IC50为7.8±0.27μM）相比，化合物和分别表现出显著的BuChE抑制潜力，IC50分别为5.3±1.23和17.2±0.47μM，化合物表现出比标准毒扁豆碱更强的BuChE抑制潜力。活性化合物和在2-OH和10-OH位置有酰基，这可能是其具有抑制潜力的原因，因为其他产物中不存在这种取向。对和产物的研究表明，由于配体与BuChE活性位点的稳定结合，对接能量得分分别为-18.8779 kcal/mol和-23.1159 kcal/mol，从而具有较高的抑制潜力。随后，具有强大BuChE抑制活性的化合物可能是阿尔茨海默病药物开发的潜在候选药物。
