Design, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agents

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dc.AffiliationOctober University for modern sciences and Arts (MSA)
dc.contributor.authorEl-Helby A.G.A.
dc.contributor.authorAyyad R.R.
dc.contributor.authorSakr H.M.
dc.contributor.authorAbdelrahim A.S.
dc.contributor.authorEl-Adl K.
dc.contributor.authorSherbiny F.S.
dc.contributor.authorEissa I.H.
dc.contributor.authorKhalifa M.M.
dc.contributor.otherPharmaceutical Chemistry Department
dc.contributor.otherFaculty of Pharmacy (Boys)
dc.contributor.otherAl-Azhar University
dc.contributor.otherCairo
dc.contributor.other11884
dc.contributor.otherEgypt; Pharmaceutical Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherDelta University for Science and Technology
dc.contributor.otherGamasa
dc.contributor.otherDakahlia
dc.contributor.otherEgypt; Organic Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherAl-Azhar University (Boys)
dc.contributor.otherCairo
dc.contributor.other11884
dc.contributor.otherEgypt; Organic Chemistry Department
dc.contributor.otherFaculty of Pharmacy
dc.contributor.otherOctober University for Modern Science and Arts (MSA)
dc.contributor.other6th October City
dc.contributor.other11787
dc.contributor.otherEgypt
dc.date.accessioned2020-01-09T20:41:23Z
dc.date.available2020-01-09T20:41:23Z
dc.date.issued2017
dc.descriptionScopus
dc.description.abstractIn view of their expected anticonvulsant activity, some novel derivatives of 2,3-dihydrophthalazine-1,4-dione 4�22 were designed, synthesized and evaluated using pentylenetetrazole (PTZ) and picrotoxin as convulsion-inducing models. Moreover, the most active compounds were tested against electrical induced convulsion using maximal electroshock (MES) models of seizures. Most of the tested compounds showed considerable anticonvulsant activity in at least one of the anticonvulsant tests. Compounds 13 and 14g were proved to be the most potent compounds of this series with relatively low toxicity in the median lethal dose test when compared with the reference drug. Molecular modeling studies were done to verify the biological activity. The obtained results showed that the most potent compounds could be useful as a template for future design, optimization, and investigation to produce more active analogues. 2016 Elsevier B.V.en_US
dc.description.urihttps://www.scimagojr.com/journalsearch.php?q=24642&tip=sid&clean=0
dc.identifier.doihttps://doi.org/10.1016/j.molstruc.2016.10.052
dc.identifier.doiPubMed ID :
dc.identifier.issn222860
dc.identifier.otherhttps://doi.org/10.1016/j.molstruc.2016.10.052
dc.identifier.otherPubMed ID :
dc.identifier.urihttps://t.ly/0E37l
dc.language.isoEnglishen_US
dc.publisherElsevier B.V.en_US
dc.relation.ispartofseriesJournal of Molecular Structure
dc.relation.ispartofseries1130
dc.subject2,3-Dihydrophthalazine-1,4-dioneen_US
dc.subjectAnticonvulsanten_US
dc.subjectGABA-Aen_US
dc.subjectMolecular modelingen_US
dc.subjectBioactivityen_US
dc.subjectDrug dosageen_US
dc.subjectMolecular modelingen_US
dc.subject2,3-Dihydrophthalazine-1,4-dioneen_US
dc.subjectActive compoundsen_US
dc.subjectAnticonvulsanten_US
dc.subjectAnticonvulsant activityen_US
dc.subjectBiological evaluationen_US
dc.subjectMedian lethal doseen_US
dc.subjectMolecular modeling studiesen_US
dc.subjectPotent compoundsen_US
dc.subjectDrug productsen_US
dc.titleDesign, synthesis, molecular modeling and biological evaluation of novel 2,3-dihydrophthalazine-1,4-dione derivatives as potential anticonvulsant agentsen_US
dc.typeArticleen_US
dcterms.isReferencedBySarro, G.D., Gitto, R., Russo, E., Ibbadu, G.F., Barreca, M.L., Luca, L.D., Chimirri, A., AMPA receptor antagonists as potential anticonvulsant drugs (2005) Curr. Top. Med. Chem., 5 (1), pp. 31-42; Kwan, P., Sander, J., The natural history of epilepsy: an epidemiological view (2004) J. Neurol. Neurosurg. Psychiatry, 75 (10), pp. 1376-1381; Nelson, L.P., Savelli-Castillo, I., New antiepileptic agents (2004) Pediatr. Dent., 26 (1), pp. 58-62; Da Settimo, A., Primofiore, G., Da Settimo, F., Marini, A.M., Novellino, E., Greco, G., Gesi, M., Lucacchini, A., N'-Phenylindol-3-ylglyoxylohydrazide derivatives: synthesis, structure-activity relationships, molecular modeling studies, and pharmacological action on brain benzodiazepine receptors (1998) J. Med. Chem., 41 (20), pp. 3821-3830; Huang, Q., He, X., Ma, C., Liu, R., Yu, S., Dayer, C.A., Wenger, G.R., Cook, J.M., Pharmacophore/receptor models for GABAA/BzR subtypes (?1?3?2, ?5?3?2, and ?6?3?2) via a comprehensive ligand-mapping approach (2000) J. Med. Chem., 43 (1), pp. 71-95; He, X., Zhang, C., Cook, J., Model of the BzR binding site: correlation of data from site-directed mutagenesis and the pharmacophore/receptor model (2001) Med. Chem. Res., 10 (5), pp. 269-308; Zhang, W., Koehler, K., Zhang, P., Cook, J., Development of a comprehensive pharmacophore model for the benzodiazepine receptor (1995) Drug Des. Discov., 12 (3), pp. 193-248; El Helby, A.A., Amin, M., Ibrahim, M.K., Ayyad, R.R., Synthesis and Pharmacological activity of some new derivatives of 1,4 (2H,3H) Phthalazindione (2002) Azhar J. Pharm. Sci., 29, pp. 36-44; Zayed, M., Ayyad, R., Evaluation of the anticonvulsant activity of 6-(4-chlorophenyoxy)-tetrazolo [5, 1-a] phthalazine in various experimental seizure models in mice (2012) Arzneimittelforschung, 62, pp. 1-5; Russell, M.G., Carling, R.W., Atack, J.R., Bromidge, F.A., Cook, S.M., Hunt, P., Isted, C., Mitchinson, A., Discovery of functionally selective 7, 8, 9, 10-Tetrahydro-7, 10-ethano-1, 2, 4-triazolo [3, 4-a] phthalazines as gabaa receptor agonists at the ?3 subunit (2005) J. Med. Chem., 48 (5), pp. 1367-1383; Rollas, S., Kkgzel, S.G., Biological activities of hydrazone derivatives (2007) Molecules, 12 (8), pp. 1910-1939; Ayyad, R.R., Mansour, A., Synthesis and biological evaluation of novel iodophthalazindione derivatives as anticonvulsant agents (2004) Azhar J. Pharm. Sci., 50, pp. 1-6; Woodbury, L.A., Davenport, V.D., Design and use of a new electroshock seizure apparatus, and analysis of factors altering seizure threshold and pattern (1952) Arch. Int. de pharmacodynamie de Ther., 92 (1), pp. 97-107; White, H.S., General principles: experimental selection, quantification, and evaluation of antiepileptic drugs (1995) Antiepileptic drugs, pp. 99-110; Baviskar, B., Shiradkar, M., Khadabadi, S., Deore, S., Bothara, K., Synthesis of thiazolyltriazole substituted azetidinones as antimicrobial agents (2011) Indian J. Chem. Part B Org. Incl. Med., 50 (3), p. 321; El-Kerdawy, M.M., El-Bendary, E.R., Alaa, A.-M., El-Wasseef, D.R., El-Aziz, N.I.A., Synthesis and pharmacological evaluation of novel fused thiophene derivatives as 5-HT 2A receptor antagonists: molecular modeling study (2010) Eur. J. Med. Chem., 45 (5), pp. 1805-1820; Warren, G.L., Andrews, C.W., Capelli, A.-M., Clarke, B., LaLonde, J., Lambert, M.H., Lindvall, M., Senger, S., A critical assessment of docking programs and scoring functions (2006) J. Med. Chem., 49 (20), pp. 5912-5931; Ci, S., Ren, T., Su, Z., Investigating the putative binding-mode of GABA and diazepam within GABAA receptor using molecular modeling (2008) Protein J., 27 (2), pp. 71-78; Richter, L., de Graaf, C., Sieghart, W., Varagic, Z., Mrzinger, M., de Esch, I.J., Ecker, G.F., Ernst, M., Diazepam-bound GABAA receptor models identify new benzodiazepine binding-site ligands (2012) Nat. Chem. Biol., 8 (5), pp. 455-464; Cody, V., Schwalbe, C.H., Structural characteristics of antifolate dihydrofolate reductase enzyme interactions (2006) Crystallogr. Rev., 12 (4), pp. 301-333; Zhao, Y.H., Abraham, M.H., Le, J., Hersey, A., Luscombe, C.N., Beck, G., Sherborne, B., Cooper, I., Rate-limited steps of human oral absorption and QSAR studies (2002) Pharm. Res., 19 (10), pp. 1446-1457; Lipinski, C.A., Lombardo, F., Dominy, B.W., Feeney, P.J., Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings (2012) Adv. Drug Deliv. Rev., 64, pp. 4-17; Allinger, N.L., Conformational analysis. 130. MM2. A hydrocarbon force field utilizing V1 and V2 torsional terms (1977) J. Am. Chem. Soc., 99 (25), pp. 8127-8134; Yang, S.-Y., Pharmacophore modeling and applications in drug discovery: challenges and recent advances (2010) Drug Discov. Today, 15 (11), pp. 444-450; Ekins, S., Mestres, J., Testa, B., In silico pharmacology for drug discovery: methods for virtual ligand screening and profiling (2007) Br. J. Pharmacol., 152 (1), pp. 9-20; Ekins, S., Mestres, J., Testa, B., In silico pharmacology for drug discovery: applications to targets and beyond (2007) Br. J. Pharmacol., 152 (1), pp. 21-37; Vijayan, R., Ghoshal, N., Structural basis for ligand recognition at the benzodiazepine binding site of GABA A ?3 receptor, and pharmacophore-based virtual screening approach (2008) J. Mol. Graph. Model., 27 (3), pp. 286-298; Hansch, C., Bjrkroth, J., Leo, A., Hydrophobicity and central nervous system agents: on the principle of minimal hydrophobicity in drug design (1987) J. Pharm. Sci., 76 (9), pp. 663-687; Lien, E., Tong, G., Chou, J., Lien, L., Structural requirements for centrally acting drugs I (1973) J. Pharm. Sci., 62 (2), pp. 246-250; Lien, E.J., Liao, R.C., Shinouda, H., Quantitative structure-activity relationships and dipole moments of anticonvulsants and CNS depressants (1979) J. Pharm. Sci., 68 (4), pp. 463-465; Ulrich, R.M., Miller, J., Threshold estimation in two-alternative forced-choice (2AFC) tasks: the SpearmanKrber method (2004) Percept. Psychophys., 66, p. 517; Crivori, P., Cruciani, G., Carrupt, P.-A., Testa, B., Predicting blood-brain barrier permeation from three-dimensional molecular structure (2000) J. Med. Chem., 43 (11), pp. 2204-2216; Dunham, N., Miya, T., A note on a simple apparatus for detecting neurological deficit in rats and mice (1957) J. Am. Pharm. Assoc., 46 (3), pp. 208-209; Li, Z., Huang, H., Sun, H., Jiang, H., Liu, H., Microwave-assisted efficient and convenient synthesis of 2, 4 (1 H, 3 H)-quinazolinediones and 2-thioxoquinazolines (2008) J. Comb. Chem., 10 (3), pp. 484-486; Rogawski, M.A., Point counterpoint: do interictal spikes trigger seizures or protect against them? (2006) Epilepsy Curr., 6 (6), pp. 197-198; Lscher, W., Nolting, B., The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. IV (1991) Prot. indices Epilepsy Res., 9 (1), pp. 1-10; Zappala, M., Grasso, S., Micale, N., Zuccala, G., Menniti, F.S., Ferreri, G., De Sarro, G., De Micheli, C., 1-Aryl-6, 7-methylenedioxy-3H-quinazolin-4-ones as anticonvulsant agents (2003) Bioorg. Med. Chem. Lett., 13 (24), pp. 4427-4430
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