Abstract
Eighteen novel 6,8-(dibromo/unsubstituted)-2-(methyl/phenyl)-3-(4-(5-(substitutedphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl)phenyl)-quinazolin-4(3H)-ones 4a–4r were designed and synthesized in good yield. Antiepileptic screening of the title compounds was performed using MES and scPTZ seizures tests while the neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 4d, 4e, 4p, 4q, and 4r were found active in MES model, while 4a, 4d, 4f, 4m, and 4p showed significant antiepileptic activity in scPTZ model. Further, all these eight compounds were administered to rats and compounds 4e, 4p, and 4q showed better activity than Phenytoin in oral route. Among these compounds 4p revealed protection in MES after i.p. administration at a dose of 30 mg/kg (0.5 h) and 100 mg/kg (4 h). The compound 4p also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abdel Gawad NM, Georgey HH, Youssef RM, El-Sayed NA (2010) Synthesis and antitumor activity of some 2,3-disubstituted-quinazolin-4(3H)-ones and 4,6-disubstituted-1,2,3,4-tetrahydro quinazolin-2H-ones. Eur J Med Chem 45:6058–6067
Abdel-Aziz M, El-Din AG, Hassan AA (2009) Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur J Med Chem 44:3480–3487
Alagarsamy V, Rajasolomon V, Vanikavitha G, Paluchamy V, Ravi Chandran M, Arnold Su** A, Thangathirupathi A, Amuthalakshmi S, Revathi R (2002) Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl 3-substituted quinazolin-4(3H)-ones. Biol Pharm Bull 25:1432–1435
Alagarsamy V, Muruganantham G, Venkateshaperumal R (2003) Synthesis, analgesic, antiinflammatory and antibacterial activities of some novel 2-methyl-3-substituted quinazolin-4(3H)-ones. Biol Pharm Bull 26:1711–1714
Alagarsamy V, Rajasolomon V, Meena R, Ramseshu KV (2005) Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-butyl-3-substituted quinazolin-4-(3H)-ones. Biol Pharm Bull 28:1091–1094
Alam O, Mullick P, Verma SP, Gilani SJ, Khan SA, Siddiqui N, Ahsan W (2010) Synthesis, anticonvulsant and toxicity screening of newer pyrimidine semicarbazone derivatives. Eur J Med Chem 45:2467–2472
Bell GS, Sander JW (2002) CPD-education and self-assessment the epidemiology of epilepsy: the size of the problem. Seizure 10:306–316
Berk M, Segal J, Janet L, Vorster M (2001) Emerging options in the treatment of bipolar disorders. Drugs 61:1407–1414
Bruno-Blanch L, Galvez J, Garcia-Domenach R (2003) Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity. Bioorg Med Chem Lett 13:2749–2754
Deng XQ, Wei CX, Li FN, Sun ZG, Quan ZS (2010) Design and synthesis of 10-alkoxy-5,6-dihydro-triazolo-[4,3-d]benzo-[f]-[1,4]oxazepine derivatives with anticonvulsant activity. Eur J Med Chem 45:3080–3086
Dinakaran M, Selvam P, Declercq E, Sridhar SK (2003) Synthesis, antiviral and cytotoxic activity of 6-bromo-2,3-disubstituted-4(3H)-quinazolinones. Biol Pharm Bull 26:1278–1282
Duncan JS (2002) The promise of new antiepileptic drugs. Br J Clin Pharmacol 53:123–131
Dunham MS, Miya TA (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Sci 46:208–209
Estrada E, Pena A (2000) In silico studies for the rational discovery of anticonvulsant compounds. Bioorg Med Chem 8:2755–2770
Karakurt A, Ozalp M, Isik S, Stables JP, Dalkara S (2010) Synthesis, anticonvulsant and antimicrobial activities of some new 2-acetylnaphthalene derivatives. Bioorg Med Chem 8:2902–2911
Kini S, Gandhi AM (2008) Novel 2-pyrazoline derivatives as potential antibacterial and antifungal agents. Indian J Pharma Sci 70:105–108
Kumar P, Shrivastava B, Pandeya SN, Stables JP (2011) Design, synthesis and potential 6 Hz psychomotor seizure test activity of some novel 2-(substituted)-3-{[substituted]amino}-quinazolin-4(3H)-one. Eur J Med Chem 46:1006–1018
Lopes Lima JM (2000) The new drugs and the strategies to manage epilepsy. Curr Pharm Design 6:873–878
Mohamed MS, Kamel MM, Kassem EMM, Abotaleb N, Abd El-moez SL, Ahmed MF (2010) Novel 6,8-dibromo-4(3H)quinazolinone derivatives of antibacterial and antiungal activities. Eur J Med Chem 45:3311–3319
Olfert ED, Cross BM, McWilliam AA (1993) Guide to the care and use of experimental animals, vol 1, 2nd edn. Canadian Council of Animal Care, Ottawa
Ozdemir Z, Kandilci HB, Gumusel B, Calis U, Bilgin AA (2007) Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-furyl)-pyrazoline derivatives. Eur J Med Chem 42:373–379
Ozdemir Z, Burak KH, Gumusel B, Calis U, Biligin AA (2008) Synthesis and studies on antidepressant and anticonvulsant activities of some 3-(2-thienyl)pyrazoline derivatives. Arch Pharm 341:701–707
Pattan SR, Krishna Reddy VV, Manvi FV, Desai BG, Bhat AR (2006) Synthesis of N-3(4-(4-chlorophenyl thiazole-2-yl)-(2-(amino)-methyl)-quinazoline-4(3H)-one and their deri-va-ti-ves for antitubercular activity. Indian J Chem 45B:1778–1781
Pollard JR, French J (2006) Antiepileptic drugs in development. Lancet Neurol 5:1064–1067
Rajak H, Deshmukh R, Aggarwal N, Kashaw S, Kharya MD, Mishra P (2009) Synthesis of novel 2,5-disubstituted-1,3,4-thiadiazoles for their potential anticonvulsant activity: pharmacophoric model studies. Arch Pharm 342:453–461
Shukla JS, Shukla R (1989) Synthesis of 4-(5-substituted arylidine 4-thiazolidinone 2-thione)-6,8-substituted quinazolines as potential antihelmintic agents. J Indian Chem Soc 66:209–210
Spear BB (2001) Pharmacogenetics and antiepileptic drug. Epilepsia 42:31–34
Stefan H, Feuerstein TJ (2007) Novel anticonvulsant drugs. Pharmacol Ther 113:165–183
Swinyard EA, Clark LD, Miyahara JT, Wolf HH (1961) Studies on the mechanism of amphetamine toxicity in aggregated mice. J Physiol 132:97–102
White HS, Johnson M, Wolf HH, Kupferberg HJ (1995) The early identification of anticonvulsant activity: the role of maximal electroshock and subcutaneous pentylenetetrazole seizure models. Ital J Neurol Sci 16:73–77
Woodbury LA, Davenport VD (1952) Design and use of a new electroshock apparatus, and analysis of factors altering seizure threshold and pattern. Arch Int Pharmacodyn Ther 92:97–107
Yogeeswari P, Sriram D, Thirumurugan R, Raghavendran JV, Sudhan K, Pavana RK, Stables JP (2005) Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: hybrid pharmacophore based design. J Med Chem 48:6202–6211
Acknowledgments
The authors gratefully acknowledge the Central Instrumentation Facility, IIT Chennai, India for the spectral analysis of the compounds used in this study. The authors are also wish to thank the management of Bapatla college of Pharmacy for providing infrastructure facilities to carry out this research work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Alagarsamy, V., Saravanan, G. Synthesis and anticonvulsant activity of novel quinazolin-4(3H)-one derived pyrazole analogs. Med Chem Res 22, 1711–1722 (2013). https://doi.org/10.1007/s00044-012-0169-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-012-0169-9