Central Bringing Excellence in Open Access   Annals of Medicinal Chemistry and Research Cite this article: Santiago-Ruiz S, Polverini E, Manjarrez J, Espinoza KA, Reynoso E, et al. (2016) Virtual Screening of Putative Anticonvulsant Hydantoin Derived Drugs and Biological Evaluation. Ann Med Chem Res 2(1): 1016. *Corresponding author Ig na c io A. Rive ro , C e ntro d e G ra d ua d o s e Inve stig a c ió n, Instituto Te c no ló g ic o d e Tijua na , P.O . Bo x 1166, 22000, Tijuana, B.C. Méxic o, Tel: 52-664-6233772; Submitte d: 16 August 2016 Accepted: 05 O c to b e r 2016 Publishe d: 07 O c to b e r 2016 ISSN: 2378-9336 Copyright © 2016 Rive ro e t a l. OPEN ACCESS Ke ywo rds • Antic o nvulsa nt • Hyd a nto in • Pip e rid ine shyd a nto ins • Ep ile p sy Research Article Virtual Screening of Putative Anticonvulsant Hydantoin Derived Drugs and Biological Evaluation Sandy Santiago-Ruiz 1 , Eugenia Polverini 2 , Joaquin Manjarrez 3 , Karla A. Espinoza 1 , Edgar Reynoso 1 , and Ignacio A. Rivero 1 * 1 Centro de Graduados e Investigación, Instituto Tecnológico de Tijuana, México 2 Department of Physics and Earth Sciences, University of Parma, Italy 3 Departmento de Formación Reticular del Instituto de Neurología y Neurocirugía, Nacional de Neurología y Neurocirugía, México Abstract It has been found that derivatives of benzyl N-piperidin-4-one have similar effect than phenytoin drug as an anticonvulsant for the treatment of epilepsy according to docking simulation studies. This is due to the similar binding mode in these chemicals. In this study, a series of six N-piperidinespirohydantoins derivatives were prepared by Bucherer-Bergs reaction, from corresponding N-piperidin-4-ones derivatives benzyl and phenethyl groups, substituted in the aromatic ring with metoxy and nitro groups. The hydantoins were evaluated for anticonvulsant activity with maximal electroshock (MES) induced method in vivo in male Wistar rats in the treatment of epilepsy. ABBREVIATIONS MES: Maximal Electro Shock; AEDs: Anti Epileptic Drugs; CASH: Cycloalkanespirohydantoins; ADT: Autodock Tools; PSH: Piperidinespirohydantoins; TLC: Thin-Layer Chromatography; IR: Infrared Spectra; TMS: Tetramethylene Silane; MS: Mass Spectra; ESI-MS: Electrospray Ionization Mass Spectra; LC/MSD: Liquid Chromatography/ Mass Spectra Detector INTRODUCTION The search for new chemical compounds that have biological activity, efficiency, effectiveness, reproducibility, stability, and security, has become paramount to the constant improvements on current medication. This is important because of a trend in patients of developing resistance to outdated and sometimes even current medication creating a constant need for more innovative pharmaceutical products. Neurodegenerative diseases have been a huge challenge for the development of new drugs, since many of them are not attractive from a commercial point of view. This is the case with epilepsy, which is one of many diseases that require lifelong treatment for the patient to remain in a controlled manner and to be allowed to do all their independent normal activities [1]. Epilepsy is the most common neurological disorder throughout the world. It is characterized by current unpredictable epileptic seizures, muscle spasms, physical injury, damage to the brain, and unconsciousness, to name a few symptoms that manifest within this disease. As thus, there exists a need for the development of new anti seizure medication with improved efficacy and tolerability, as several of the currently available antiepileptic drugs (AEDs) have been associated with undesirable side effects [2-4]. There are several drugs that are able to control this disease; one of the most used is the phenytoin, which contains a hydantoin ring. Hydantoin (imidazolidine-2,4-dione) moiety constitutes an attractive and multifaceted pharmacological scaffold present in several drugs [7]. This small and rigid heterocyclic backbone, has potential to act on various pharmacological targets. Hydantoin-1,3-imidazolidinedione derivatives [5,6] Figure (1) exhibit diverse and interesting pharmacological properties [7,8]. Several such derivatives (phenytoin, mephenythoin, norantoin, methetoin, ethotoin, osphenytoin) are renowned anticonvulsive drugs [9,10] (Table 1). The anticonvulsant activity of hydantoins has been known since 1938 when Merrit and Putman discovered that 5,5-diphenylhydantoin (phenytoin) Figure (2) showed anti- epileptic acivity [11]. Phenytoin acts on brain by reducing electrical conductance among neurons by stabilizing the inactive state of voltage gated sodium channel [12-14] (Table 2).