Design,synthesis, in vivo and in silico evaluation of phenacyl triazole hydrazones as new anticonvulsant agents |
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| Institution: | 1. Student Research Committe, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;3. Department of Medicinal Chemistry and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran;4. Student Research Committee, Ramsar International Branch, Mazandaran University of Medical Sciences, Iran;1. Department of Pharmaceutical Chemistry, School of Pharmaceutical Education & Research (Formerly, Faculty of Pharmacy), Jamia Hamdard, New Delhi 110062, India;2. Department of Pharmaceutical Chemistry, Delhi Institute of Pharmaceutical Sciences and Research (DIPSAR), Mehrauli-Badarpur Road, Pushp Vihar, Sector-3, New Delhi 110017, India;1. Department of Organic and Bioorganic Chemistry, Faculty of Pharmacy in Hradec Králové, Charles University, Akademika Heyrovského 1203, 500 05 Hradec Králové, Czech Republic;2. MTA-ELTE Research Group of Peptide Chemistry, Eötvös Loránd University, Pázmány Péter Sétány 1/A, Budapest, H-1117, P.O. Box 32, 1518 Budapest 112, Hungary;3. Laboratory for Mycobacterial Diagnostics and Tuberculosis, Regional Institute of Public Health in Ostrava, Partyzánské náměstí 7, 702 00 Ostrava, Czech Republic;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ege University, 35040 Izmir, Turkey;2. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Ege University, 35040 Izmir, Turkey;3. Institute of Pharmacy and Food Chemistry, University of Wuerzburg, Am Hubland, 97074 Wuerzburg, Germany;1. Department of Chemistry, Acharya Nagarjuna University, Nagarjuna Nagar, 522 510 Andhra Pradesh, India;2. Medicinal Chemistry and Pharmacology Division, CSIR-Indian Institute of Chemical Technology, Uppal Road, Tarnaka, Hyderabad 500007, Telangana, India;1. National University of Pharmacy, 53, Pushkinskaya st., Kharkiv, 61002, Ukraine;2. V.N.Karazin Kharkiv National University, 4 Svobody sq., Kharkiv, 61077, Ukraine;3. Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University, 8 Trubeckaya, Moscow, 119991, Russia;4. Federal State Budgetary Institution “Scientific Centre for Expert Evaluation of Medicinal Products”, Petrovsky boulevard 8. bld. 2, Moscow, 127051, Russia;1. Department of Pharmacology and Toxicology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran;2. Department of Chemistry, Tarbiat Modares University, Tehran, Iran;3. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran;4. Biomaterial and Medicinal Chemistry Research Center, Aja University of Medical Science, Tehran, Iran |
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| Abstract: | A series of phenacyl triazole hydrazones 3 have been designed based on the hybridization of (arylalkly)triazole and aroyl hydrazone scaffolds as new anticonvulsant agents. The target compounds 3 were easily synthesized from appropriate phenacyl triazoles and aryl acid hydrazides and characterized by IR, NMR and Mass spectroscopy. The in vivo anticonvulsant evaluation of synthesized compounds by using MES and PTZ tests revealed that they are more effective in MES model respect to PTZ test. All compounds showed 33–100% protection against MES-induced seizures at the dose of 100 mg/kg. However, the isonicotinic acid hydrazide derivative 3h showed the best profile of activity in both models. Molecular docking studies of compound 3h with different targets (NMDA, AMPA, GABAA and sodium channel), postulated that the compound acts mainly via GABAA receptors. In silico molecular properties predictions indicated that all compounds have favourable oral bioavailability and BBB permeability. |
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| Keywords: | Arylalkyl azole 1 2 4-Triazole Hydrazone Anticonvulsant agents |
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