Docking Studies of Phthalimide Pharmacophore as a Sodium Channel Blocker
- سال انتشار: 1392
- محل انتشار: مجله علوم پایه پزشکی ایران، دوره: 16، شماره: 9
- کد COI اختصاصی: JR_IJBMS-16-9_011
- زبان مقاله: انگلیسی
- تعداد مشاهده: 321
نویسندگان
Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
Department of Medicinal Chemistry, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran
چکیده
Objective(s): Recently, phthalimide derivatives were designed based on ameltolide and thalidomide as they possess a similar degree of anticonvulsant potency due to their phenytoin-like profile. The ability of phthalimide pharmacophore to interact with neuronal voltage-dependent sodium channels was studied in the batrachotoxin affinity assay. Therefore, in the present study, a series of ۱۹ compounds of phthalimide pharmacophore possessing a variety of substituents (NO۲, NH۲ , Me, Cl, COOH, MeO) at ۲-, ۳-, and ۴- position of the N-phenyl ring and N-(۳-amino-۲-methylphenyl) succinimide, were subjected to docking studies in order to inhibit voltage-gated sodium channels. Materials and Methods : Chemical structures of all compounds were designed using HYPERCHEM program and Conformational studies were performed through semi-empirical molecular orbital calculations method followed by PM۳ force field. Total energy gradient calculated as a root mean square (RMS) value, until the RMS gradient was ۰.۰۱ kcal mol-۱. Among all energy minima conformers, the global minimum of compounds was used in docking calculations. Using a model of the open pore of Na channels, docking study was performed by AUTODOCK۴.۲ program. Results : Docking studies have revealed that these types of ligands interacted mainly with II-S۶ residues of NaV۱.۲ through making hydrogen bonds and have additional hydrophobic interactions with domain I, II, III and IV in the channel's inner pore. Conclusion : These computational studies have displayed that these compounds are capable of inhibiting Na channel, efficiently.کلیدواژه ها
Anticonvulsant Docking Molecular modeling Na channel Phthalimideاطلاعات بیشتر در مورد COI
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