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ogy iol : Op r B e a n l A u c c c e l e Ajeet et al., Mol Biol 2018, 7:2 o s s M Molecular Biology: Open Access DOI: 10.4172/2168-9547.1000206 ISSN: 2168-9547 Research Article Open Access Design, Synthesis and Pharmacological Evaluation of Sulfonamide Derivatives Screened Against Maximal Electroshock Seizure Test Ajeet1*, Kumar A2 and Mishra AK1 1Drug Design Laboratory, School of Pharmaceutical Sciences, IFTM University, Moradabad, India 2Department of Pharmaceutical Chemistry, S. D. College of Pharmacy and Vocational Studies,Muzaffarnagar , India Abstract A series of substituted 4-amino-benzene sulfonamides were designed, keeping in view the structural requirement of pharmacophore. Lipinski rule of five has also been calculated; failure to Lipinski rule was not observed. The synthesized compounds were evaluated for anticonvulsant. Docking was performed through AutoDock Vina. Molecules have been screened out through docking. Compounds were synthesized and characterized through IR, 1HNMR, 13C NMR, Mass and elemental analysis. The anticonvulsant activity of the synthesized compounds was assessed using the MES model. In-silico biological activity spectrum, toxicological studies, predicted oral rat LD50 and possible mechanism of action were investigated. The compound, 4-[2-(4-Acetyl-phenylamino)-ethyl]-benzenesulfonamide (K23) is found most active among the synthesized compounds. Keywords: Anticonvulsant; Sulfonamide; Docking; In-silico studies; activity-relationship (SAR) models; (iv) Ligand-protein docking studies Synthetic compounds of designed compounds; (v) Toxicity estimation of designed compound and (vi) Evaluation of possible pharmacological properties designed Introduction compounds. The newly designed compounds, which follow the criteria considered in multiple computational studies, are preceded for Epilepsy is one of the serious disorders with no age, sex or racial synthesis, structural elucidation and further experimental evaluation of boundaries. Epilepsy imposes a large economic burden on health care activities. systems of countries. There is also a hidden burden associated with stigma and discrimination against the patient and even their family In this paper, we have designed and synthesized compounds in the community, workplace, and home. In general, the patients with as carbonic anhydrase inhibitors, keeping in view the structural epilepsy suffer severe emotional distress, behavioral disorders and requirement of pharmacophore. All the designed compounds were extreme social isolation [1]. initially gone through in-silico screening like Lipinski rule, QSAR modeling & screening and docking studies. The screened compounds Epilepsy is usually associated with recurrent seizures. This implies were then synthesized and gone through analytical studies like IR, NMR that epilepsy is an ancient disorder; indeed, in all civilizations it can be and Mass spectroscopy. After that all the synthesized compounds were traced as far back as medical records exist. In fact, epilepsy is a disorder treated for pharmacological screening. An In-silico biological activity that can occur in all mammalian species, probably more frequently spectrum, toxicological studies, predicted oral rat LD50, possible as brains have become more complex. Epilepsy is also remarkably mechanism of action and SAR studies were also investigated. uniformly distributed around the world [2]. Steps followed for completing the current research work is shown Among the reported potential agents to treat the epilepsy, in following illustration Figure 1. sulphonamides are important and their significance cannot be ignored. Sulphonamides are of high attention for various pharmacological Materials and Methods importance, as it is reported for chiefly anticonvulsant [3,4], antitubercular [5,6] and antimicrobial activities [7,8]. For all these Designing of molecules activities, the suphonamide derivatives are reported with multiple Identification of pharmacophoric groups was done from the scaffolds such as Sulfonamides incorporating Valproyl derivatives, structures of well-known anticonvulsants. The structures of well-known Sulfamates, Sulfamides, Thiazolidin derivatives, Aminobenzamides, anticonvulsants and identified pharmacophore are presented in Table 1 Beta-Ketosulfonamide etc [3-8]. [9,10]. The essential structural features which could be responsible for an interaction with the active site were a hydrophobic (HP) unit, an electron Being inspired from the previous developments, there is always donor (D) group, and a hydrogen donor/acceptor (HD/HA) unit. an enthusiasm to design of novel sulphonamide with many scaffolds and to evaluate their possible pharmacological properties as well as mechanism of action. These novel designs will support for future drug developments for multiple diseases in human health care. There is *Corresponding author: Ajeet, Drug Design Laboratory, School of Pharmaceutical always a chance to get a potential compound on hit and trial basis for Sciences, IFTM University, Moradabad, Uttar Pradesh, India, Tel: +91-9236817425; design and synthesis of novel compounds. Beyond this, at present multi- E-mail: [email protected] disciplinary protocols are being suggested to screen the designed-only Received February 06, 2018; Accepted February 21, 2018; Published February compounds through computational methods to get the possibility of 28, 2018 pharmacological importance of compounds prior to their synthesis and Citation: Ajeet, Kumar A, Mishra AK (2018) Design, Synthesis and Pharmacological in-vitro experiments. Sequential computational procedures include: (i) Evaluation of Sulfonamide Derivatives Screened Against Maximal Electroshock Collection of information about scaffolds, linkers and side-groups for Seizure Test. Mol Biol 7: 206. doi: 10.4172/2168-9547.1000206 possible novel compound; (ii) Structural designing of location specific Copyright: © 2018 Ajeet, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted derivative combinations with one or more scaffold; (iii) Virtual- use, distribution, and reproduction in any medium, provided the original author and screening of activity of designed compounds through structure- source are credited. Mol Biol, an open access journal Volume 7 • Issue 2 • 1000206 ISSN: 2168-9547 Citation: Ajeet, Kumar A, Mishra AK (2018) Design, Synthesis and Pharmacological Evaluation of Sulfonamide Derivatives Screened Against Maximal Electroshock Seizure Test. Mol Biol 7: 206. doi: 10.4172/2168-9547.1000206 Page 2 of 10 D HA HP O N N HP S D N O H D NH2 HD Albutoin Carbamazepine HD H H OH HD D N N N H H O D HA H N N N Figure 1: Complete steps followed during research work. HA HP H Cl O HA Gabapentin Cl HA Lamotrigine O N NH HD HA H N 2 S O O O HA HD HA O O D Ethosuximide N NH Zonisamide HD O O Methylphenobarbital N OH HA O HD D H N H S HA F N HD H HP HN O D Cl Cl Progabide Ralitoline D D Basic identified pharmacophore H O N H Table 1: Pharmacophoric pattern of well-known anticonvulsants. N HN HD NH O H HA Docking studies HA HD O Docking tool: Docking was performed with AutoDock Vina HP (PyRx-Python Prescription 0.8) docking software [11]. It is virtual HP screening software for computational drug discovery that can be used to screen libraries of compounds against potential drug targets. It Phenytoin Remacemide enables medicinal chemists to run virtual screening form any platform and helps users in every steps of this process from data preparation to job submission and analysis of the results [12]. Receptor: Lyase (Oxo-acid)-Human Carbonic Anhydrase-I. Mol Biol, an open access journal Volume 7 • Issue 2 • 1000206 ISSN: 2168-9547 Citation: Ajeet, Kumar A, Mishra AK (2018) Design, Synthesis and Pharmacological Evaluation of Sulfonamide Derivatives Screened Against Maximal Electroshock Seizure Test. Mol Biol 7: 206. doi: 10.4172/2168-9547.1000206 Page 3 of 10 Experimental: All the chemicals and solvents, purchased from Merck (India), Spectrochem (India), Sigma-Aldrich (India), Hi-Media H (India) and S.D. Fine (India) were used without further purification. N C SO NH Thin layer chromatographic (TLC) analysis of compounds was Cn n 2 2 performed on silica gel G coated glass plates. The adsorbent silica gel Cl H G was coated to a thickness of about 0.3 mm on previously cleaned TLC plates of 20x5 cm2 using conventional spreader. The plates were placed in hot air oven at 105°C for 30 min. The solutions of compounds R were applied as a spot on the activated plate about 2 cm above from the lower edge. The mobile phases were selected according to the polarity of compounds. H R N Cn Melting points were determined by using open capillary melting HCl gas Cn point apparatus and are reported uncorrected. The 1H-NMR spectra were recorded on Avance-III, Bruker, 400 MHz High Resolution NMR spectrometer and C13-NMR were recorded with Avance-III, Bruker, 100 MHz. Signals were described as singlet (s), doublet (d), triplet (t) SO2NH2 and multiplet (m). FT-IR spectra (KBr) were recorded on a Perkin- Common reaction mechanism of schemes employed. Elmer Spectrometer BX-II spectrophotometer. The mass spectra were Figure 3: recorded on a Waters Micro-Mass ZQ 2000 mass spectrometer. Synthetic scheme in 50 ml. of dry acetone. After addition, the reaction mixture was stirred for about 12 hour at room temperature and then the solvent was Shown in following illustration Figure 2. evaporated under reduced pressure. The residue was dissolved in 100 Mechanism of