SYNTHESIS AND ANTICONVULSANT ACTIVITY (CHEMO SHOCK) OF N-1(SUBSTITUTED-N-4[(4-OXO-3-PHENYL-3, 4-DIHYDRO-QUINAZOLINE-2-YLMETHYL) SEMICARBAZONES

Meena K Yadav; Laxmi Tripathi; Diptendu Goswami

doi:10.22159/ajpcr.2017.v10i4.16876

Authors

Meena K Yadav Mahatma Gandhi Institute of Pharmacy, Lucknow- Kanpur Road, Lucknow, Uttar Pradesh, India-227101
Laxmi Tripathi Moradabad Educational Trust, Group of Institutions, Faculty of Pharmacy, Moradabad, Uttar Pradesh India-244001,
Diptendu Goswami Naraina Vidya Peeth Group of Institutions, Panki, Kanpur, Uttar Pradesh india-208020

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i4.16876

Abstract

Objective: This work is designed at finding new structure leads with potential anticonvulsant activities of 4(3H)-quinazolinone pharmacophoreÂ scaffold.

Methods: A new series of 4(3H)-quinazolinone pharmacophore was designed with substituted moieties possesses different electronic environmentÂ in the hope of developing potent and safe new effective compounds. In such fashion, in this paper, we report the synthesis and anticonvulsant activityÂ (Chemo shock) of N-1(substituted-N-4[(4-oxo-3-phenyl-3, 4-dihydro-quinazoline-2-ylmethyl) semicarbazones 3A-d (1-7), 3B-d (1-7), 3C-d (1-7),Â their chemical structure were characterized using IR, Â H-H NMR, and elemental analysis techniques. Their anticonvulsant activity was evaluated usingÂ chemicals strychnine, thiosemicarbazide and 4-aminopyridine induced seizure models at a dose of 30, 100, 300 mg/kg unto 2 hrs tests in mice. TheÂ rotarod assay was performed in mice to evaluate the neurotoxicity of the compounds.Â 1
Results: Compounds 3C (d-4), 3B (d-4), and 3A (d-4) were observed to be most feasible to act against glutamate receptor for anticonvulsant activity.

Conclusions: The results obtained revealed that numbers of novel quinazolinone semicarbazone derivatives are effective in chemical to induceÂ (chemo shock) model and showing good anticonvulsant activity.

Keywords: Quinazolinone, Semicarbazones, Strychnine, Thiosemicarbazide, 4-aminopyridine, Anticonvulsant activity, Chemo shock.

Downloads

Download data is not yet available.

Author Biographies

Meena K Yadav, Mahatma Gandhi Institute of Pharmacy, Lucknow- Kanpur Road, Lucknow, Uttar Pradesh, India-227101

Pharmacy, Associate Professor

Laxmi Tripathi, Moradabad Educational Trust, Group of Institutions, Faculty of Pharmacy, Moradabad, Uttar Pradesh India-244001,

Pharmacy, Professor

Diptendu Goswami, Naraina Vidya Peeth Group of Institutions, Panki, Kanpur, Uttar Pradesh india-208020

Pharmacy, Professor

References

Ram VJ, Farhanullah, Tripathi BK, Srivastava AK. Synthesis and antihyperglycemic activity of suitably functionalized 3H-quinazolin-4-ones. Bioorg Med Chem 2003;11(11):2439-44.

Dandia A, Singh R, Sarawgi P. Green chemical multi-component one-pot synthesis of fluorinated 2,3-disustitued quinazolin-4(3H)-ones under solvent free conditions and their anti-fungal activity. J Fluor Chem 2004;125(12):1835-40.

Carl GF, Smith ML. Phenytoin-folate interactions: Differing effects of the sodium salt and the free acid of phenytoin. Epilepsia 1992;33(2):372-5.

Kwan P, Brodie MJ. Phenobarbital for the treatment of epilepsy in the 21st century: A critical review. Epilepsia 2004;45(9):1141-9.

Shorvon SD. Drug treatment of epilepsy in the century of the ILAE: The second 50 years, 1959-2009. Epilepsia 2009;50 Suppl 3:93-130.

Foster AC, Kemp JA. Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol 2006;6(1):7-17.

Mazza M, Della Marca G, Di Nicola M, Martinotti G, Pozzi G, Janiri L, et al. Oxcarbazepine improves mood in patients with epilepsy. Epilepsy Behav 2007;10(3):397-401.

Rho JM, Donevan SD, Rogawski MA. Barbiturate-like actions of the propanediol dicarbamates felbamate and meprobamate. J Pharmacol Exp Ther 1997;280(3):1383-91.

Coyle JT, Leski M, Morrison JH. The diverse roles of L-glutamic acid in brain signal transduction. In: Davis KL, Charney D, Coyle JT, Nemeroff C, editors. Neuropsychopharmacology: The Fifth Generation of Progress. Philadelphia, PA: Lippincott, Williams & Wilkins; 2002. p. 71-90.

Hassel B, Dingledine R. Glutamate. In: Siegel GJ, Albers RW, Brady ST, Price DL, editors. Basic Neurochemistry Molecular, Cellular, and Medical Aspects. 7th ed., Ch. 15. Burlington, MA: Elsevier Academic Press; 2006. p. 267-90.

Ascher P, Nowak L. Quisqualate-and kainate-activated channels in mouse central neurones in culture. J Physiol 1988;399:227-45.

Collingridge GL, Lester RA. Excitatory amino acid receptors in the vertebrate central nervous system. Pharmacol Rev 1989;41(2):143-210.

Bliss TV, Collingridge GL. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 1993;361(6407):31-9.

Collingridge GL, Bliss TV. Memories of NMDA receptors and LTP. Trends Neurosci 1995;18(2):54-6.

Collingridge GL, Singer W. Excitatory amino acid receptors and synaptic plasticity. Trends Pharmacol Sci 1990;11(1):290-6.

Danysz W, Parsons, GG, Bresink I, Quack G. Glutamate in CNS disorders: A revived target for drug development. Drug News Perspect 1995;8:261-77.

Dingledine R, Borges K, Bowie D, Traynelis SF. The glutamate receptor ion channels. Pharmacol Rev 1999;51(1):7-61.

Gill SS, Pulido OM, Mueller RW, McGuire PF. Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart. Brain Res Bull 1998;46(5):429-34.

Hashimoto K, Shimizu E, Iyo M. Dysfunction of glia-neuron communication in the pathophysiology of schizophrenia. Curr Psychiatry Rev 2005;1:151-63.

Hashimoto K, Hattori E. Part II. Candidate gene and models. 4. Neurotransmission. In: Sawa A, McInnis MG, editors. Neurogenetics of Psychiatric Disorders. New York: Informa Healthcare; 2007. p. 81-100.

Nadler JV. Plasticity of glutamate synaptic mechanisms. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasperâ€™s Basic Mechanisms of the Epilepsies. 4th ed. Bethesda, MD: US: National Center for Biotechnology Information; 2012.

Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, et al. Glutamate receptor ion channels: Structure, regulation, and function. Pharmacol Rev 2010;62(3):405-96.

Rogawski MA. Revisiting AMPA receptors as an antiepileptic drug target. Epilepsy Curr 2011;11(2):56-63.

Lerma J, Paternain AV, RodrÃguez-Moreno A, LÃ³pez-GarcÃa JC. Molecular physiology of kainate receptors. Physiol Rev 2001;81(3):971-98.

Bleakman D. Kainate receptor pharmacology and physiology. Cell Mol Life Sci 1999;56(7-8):558-66.

Semyanov A, Kullmann DM. Kainate receptor-dependent axonal depolarization and action potential initiation in interneurons. Nat Neurosci 2001;4(7):718-23.

Ben-Ari Y, Cossart R. Kainate, a double agent that generates seizures: Two decades of progress. Trends Neurosci 2000;23(11):580-7.

Mulle C, Sailer A, PÃ©rez-OtaÃ±o I, Dickinson-Anson H, Castillo PE, Bureau I, et al. Altered synaptic physiology and reduced susceptibility to kainate-induced seizures in GluR6-deficient mice. Nature 1998;392(6676):601-5.

Vignes M, Bleakman D, Lodge D, Collingridge GL. The synaptic activation of the GluR5 subtype of kainate receptor in area CA3 of the rat hippocampus. Neuropharmacology 1997;36(11-12):1477-81.

Li H, Rogawski MA. GluR5 kainate receptor mediated synaptictransmission in rat basolateral amygdala in vitro. Neuropharmacology 1998;37(10-11):1279-86.

Wu LJ, Zhao MG, Toyoda H, Ko SW, Zhuo M. Kainate receptor-mediated synaptic transmission in the adult anterior cingulate cortex. J Neurophysiol 2005;94(3):1805-13.

Koga K, Sim SE, Chen T, Wu LJ, Kaang BK, Zhuo M. Kainate receptor-mediated synaptic transmissions in the adult rodent insular cortex. J Neurophysiol 2012;108(7):1988-98.

Cossart R, Esclapez M, Hirsch JC, Bernard C, Ben-Ari Y. GluR5 kainate receptor activation in interneurons increases tonic inhibition of pyramidal cells. Nat Neurosci 1998;1(6):470-8.

Wondolowski J, Frerking M. Subunit-dependent postsynaptic expression of kainate receptors on hippocampal interneurons in area CA1. J Neurosci 2009;29(2):563-74.

Christensen JK, Paternain AV, Selak S, Ahring PK, Lerma J. A mosaic of functional kainate receptors in hippocampal interneurons. J Neurosci 2004;24(41):8986-93.

Aroniadou-Anderjaska V, Pidoplichko VI, Figueiredo TH, Almeida-Suhett CP, Prager EM, Braga MF. Presynaptic facilitation of glutamate release in the basolateral amygdala: A mechanism for the anxiogenic and seizurogenic function of GluK1 receptors. Neuroscience 2012;221:157-69.

Smolders I, Bortolotto ZA, Clarke VR, Warre R, Khan GM, Oâ€™Neill MJ, et al. Antagonists of GLU(K5)-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nat Neurosci 2002;5(8):796-804.

Khalilov I, Hirsch J, Cossart R, Ben-Ari Y. Paradoxical anti-epileptic effects of a GluR5 agonist of kainate receptors. J Neurophysiol 2002;88(1):523-7.

Hanada T, Hashizume Y, Tokuhara N, Takenaka O, Kohmura N, Ogasawara A, et al. Perampanel: A novel, orally active, noncompetitive AMPA-receptor antagonist that reduces seizure activity in rodent models of epilepsy. Epilepsia 2011;52(7):1331-40.

Kramer LD, Satlin A, Krauss GL, French J, Perucca E, Ben-Menachem E, et al. Perampanel for adjunctive treatment of partial-onset seizures: A pooled dose-response analysis of phase III studies. Epilepsia 2014;55(3):423-31.

Gibbs JW 3rd, Sombati S, DeLorenzo RJ, Coulter DA. Cellular actions of topiramate: Blockade of kainate-evoked inward currents in cultured hippocampal neurons. Epilepsia 2000;41 Suppl 1:S10-6.

El-Azab AS, Eltahir KE. Synthesis and anticonvulsant evaluation of some new 2,3,8-trisubstituted-4(3H)-quinazoline derivatives. Bioorg Med Chem Lett 2012;22(1):327-33.

Dimmock JR, Sidhu KK, Thayer RS, Mack P, Duffy MJ, Reid RS, et al. Anticonvulsant activities of some arylsemicarbazones displaying potent oral activity in the maximal electroshock screen in rats accompanied by high protection indices. J Med Chem 1993;36(16):2243-52.

Pandeya SN, Aggarwal N, Jain JS. Evaluation of semicarbazones for anticonvulsant and sedative-hypnotic properties. Pharmazie 1999;54(4):300-2.

Pandeya SN, Ponnilavarasan I, Pandey A, Lakhan R, Stables JP. Evaluation of p-nitrophenyl substituted semicarbazones for anticonvulsant properties. Pharmazie 1999;54(12):923-5.

Yogeeswari P, Sriram D, Pandeya SN, Stables JP. 4-sulphamoylphenyl semicarbazones with anticonvulsant activity. Farmaco 2004;59(8):609-13.

Pandeya SN, Yogeeswari P, Stables JP. Synthesis and anticonvulsant activity of 4-bromophenyl substituted aryl semicarbazones. Eur J Med Chem 2000;35(10):879-86.

Krall RL, Penry JK, White BG, Kupferberg HJ, Swinyard EA. Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia 1978;19(4):409-28.

Vogel HG. Drug Discovery and Evaluation: Pharmacological Assay. New York: Berlin Springer-Verlag; 2002. p. 696-716.

Nishi A, Liu F, Matsuyama S, Hamada M, Higashi H, Nairn AC, et al. Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proc Natl Acad Sci U S A 2003;100(3):1322-7.

McGeer EG, Ikeda H, Asakura T, Wada JA. Lack of abnormality in brain aromatic amines in rats and mice susceptible to audiogenic seizure. J Neurochem 1969;16(3):945-50.

Biswajit D, Suvakanta D, Damiki L. Design and synthesis of 4-substituted quinazoline derivatives for their anticonvulsant and CNS depressant activities. Int J Pharm Pharm Sci 2017;9(1):165-72.

Hemant C, Kedar L, Poorvashree J, Sneha K, Amit N, Sanjay S. In silico: Design, synthesis and pharmacological screening of some quinazolinones as possible GABAA receptor agonists for anticonvulsant activity. Int J Pharm Pharm Sci 2012;4(2):466-9.