Synthesis, characterization & anticonvulsant activity of amide derivatives of 4-amino-1,2-naphthoquinone
Tóm tắt
In the present study, 4-amino-1,2-naphthoquinone analogues were synthesized and characterized by spectroscopic (FT-IR, 1H NMR and 13C NMR) and elemental analysis. The synthesized compounds were evaluated for anticonvulsant activity by the maximal electroshock (MES) test and subcutaneous pentylenetetrazole (sc. PTZ) test, the most widely employed seizure models for early identification of anticonvulsant candidates, whereas their neurotoxicity was examined by rotarod test. Compounds were administered to animals at different concentrations (10, 20 & 40 mg/kg) by intraperitonial (i.p.) route and the % seizure protection was measured. The pharmacological results revealed that majority of compounds were effective in MES and sc. PTZ tests. Compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)butyramide (4) and N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)-3-methylbutanamide (6) were active at the dose 40 & 20 mg/kg, respectively, while compounds N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)hexanamide (7) and 4-acetamido-N-(1,2-dihydro-1,2-dioxonaphthalen-4-yl)benzamide (10) were active at the dose 10 mg/kg and emerged as the most active compounds of the series. These compounds showed anticonvulsant effect comparable to phenytoin which was used as reference antiepileptic drug. The above-mentioned compounds have diminutive neurotoxic effects so they can move on next phase of anticonvulsant drug development.
Từ khóa
Tài liệu tham khảo
Bonifácio MJ, Sheridan RD, Parada A, Cunha RA, Patmore L, Soares-da-Silva P (2001) Interaction of the novel anticonvulsant, BIA 2–093, with voltage-gated sodium channels: comparison with carbamazepine. Epilepsia 42(5):600–608
Brodie MJ, Dichter MA (1996) Antiepileptic drugs. N Engl J Med 334(3):168–175. doi:10.1056/NEJM199601183340308
Chung Y, Quan R, Chang H, Kwon S, Kim S-J, Im Y-S, Shin K, Park K-D, Lee H-K, Choi J-K (2009) Antibacterial activity of novel naphthoquiones derivatives. Genes Genomics 31(6):429–434. doi:10.1007/BF03191856
Dalkara S, Karakurt A (2012) Recent progress in anticonvulsant drug research: strategies for anticonvulsant drug development and applications of antiepileptic drugs for non-epileptic central nervous system disorders. Curr Top Med Chem 12(9):1033–1071
Das N, Dhanawat M, Shrivastava SK (2012) An overview on antiepileptic drugs. Drug Discov Ther 6(4):178–193. doi:10.5582/ddt.2012.v6.4.178
Fieser LF, Hartwell JL (1935) The Reaction of Hydrazoic Acid with the Naphthoquinones. J Am Chem Soc 57(8):1482–1484
Gidal BE, Garnett WR (2005) Epilepsy. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM (eds) Pharmacotherapy: a pathophysiologic approach, 6th edn. McGraw-Hill, New York, p 1023
Gupta YK, Malhotra J, George B, Kulkarni SK (1999) Methods and considerations for experimental evaluation of antiepileptic drugs. Indian J Physiol Pharmacol 43(1):25–43
Hen N, Bialer M, Yagen B (2012) Synthesis and evaluation of anticonvulsant activity of novel branched alkyl carbamates. J Med Chem 55(6):2835–2845. doi:10.1021/jm201751x
Kennedy S, Dicesare JC, Sheaff RJ (2011) Topoisomerase I inactivation by a novel thiol reactive naphthoquinone. Biochem Biophys Res Commun 410(1):152–158. doi:10.1016/j.bbrc.2011.05.131
Krishnan A, Ritvik Chowdhury D (2007) Cost of antiepileptic drugs in India. Neurol Asia 12:42–43
Kupferberg HJ (1989) Antiepileptic drug development program: a cooperative effort of government and industry. Epilepsia 30 Suppl 1:S51–56; discussion S64–58
Leppik IE (1996) Contemporary Diagnosis and Management of the Patient with Epilepsy, 2nd edn. Handbooks in Health Care, Newtown
Molgaard-Nielsen D, Hviid A (2011) Newer generation antiepileptic drugs and the risk of major birth defects. JAMA 305(19):1996–2002. doi:10.1001/jama.2011.624
Mori-Yasumoto K, Izumoto R, Fuchino H, Ooi T, Agatsuma Y, Kusumi T, Satake M, Sekita S (2012) Leishmanicidal activities and cytotoxicities of bisnaphthoquinone analogues and naphthol derivatives from Burman Diospyros burmanica. Bioorg Med Chem 20(17):5215–5219. doi:10.1016/j.bmc.2012.06.055
Pandey S, Srivastava RS (2011) Synthesis and characterization of some heterocyclic schiff bases: potential anticonvulsant agents. Med Chem Res 20(7):1091–1101. doi:10.1007/s00044-010-9441-z
Perucca P, Gilliam FG (2012) Adverse effects of antiepileptic drugs. Lancet Neurol 11(9):792–802. doi:10.1016/S1474-4422(12)70153-9
Pessah N, Yagen B, Hen N, Shimshoni JA, Wlodarczyk B, Finnell RH, Bialer M (2011) Design and pharmacological activity of glycinamide and N-methoxy amide derivatives of analogs and constitutional isomers of valproic acid. Epilepsy Behav 22(3):461–468. doi:10.1016/j.yebeh.2011.08.026
Pinto AV, de Castro SL (2009) The trypanocidal activity of naphthoquinones: a review. Molecules 14(11):4570–4590. doi:10.3390/molecules14114570
Pradidphol N, Kongkathip N, Sittikul P, Boonyalai N, Kongkathip B (2012) First synthesis and anticancer activity of novel naphthoquinone amides. Eur J Med Chem 49:253–270. doi:10.1016/j.ejmech.2012.01.020
Schmidt D, Rogawski MA (2002) New strategies for the identification of drugs to prevent the development or progression of epilepsy. Epilepsy Res 50(1–2):71–78
Shukla S, Srivastava RS, Shrivastava SK, Sodhi A, Kumar P (2012a) Synthesis, characterization and antiproliferative activity of 1,2-naphthoquinone and its derivatives. Appl Biochem Biotechnol 167(5):1430–1445. doi:10.1007/s12010-012-9551-9
Shukla S, Srivastava RS, Shrivastava SK, Sodhi A, Kumar P (2012b) Synthesis, molecular docking and biological evaluation of 4-cycloalkylidineamino 1, 2-naphthoquinone semicarbazones as anticancer agents. Asian Pac J Trop Biomed 2(2 suppl):S1040–S1046. doi:10.1016/S2221-1691(12)60358-X
Sousa DPd, Nóbrega FFF, Santos CCMP, Benedito RB, Vieira YW, Uliana MP, Brocksom TJ, Almeida RNd (2011) Anticonvulsant activity of thymoquinone and its structural analogues. Rev bras farmacogn 21 (3):427–431
Tripathi L, Kumar P, Singh R, Stables JP (2012) Design, synthesis and anticonvulsant evaluation of novel N-(4-substituted phenyl)-2-[4-(substituted) benzylidene]-hydrazinecarbothio amides. Eur J Med Chem 47(1):153–166. doi:10.1016/j.ejmech.2011.10.038
Vajda JE, Graham J, Roten A, Lander CM, O’Brien TJ, Eadie M (2012) Teratogenicity of the newer antiepileptic drugs—the Australian experience. J Clin Neurosci 19:57–59. doi:10.1016/j.jocn.2011.08.003
Vogel WH (2002) Psychotropic and neurotropic activity. In: Vogel HG (ed) Drug discovery and evaluation: pharmacological assays, 2nd edn. Springer, Berlin, pp 422–423
White HS, Woodhead JH, Wilcox KS, Stables JP, Kupferberg HJ, Wolf HH (2002) Discovery and preclinical development of antiepileptic drugs, 5th edn. Lippincott Williams & Wilkins, New York, pp 36–48
Yang XH, Wen Q, Zhao TT, Sun J, Li X, Xing M, Lu X, Zhu HL (2012) Synthesis, biological evaluation, and molecular docking studies of cinnamic acyl 1,3,4-thiadiazole amide derivatives as novel antitubulin agents. Bioorg Med Chem 20(3):1181–1187. doi:10.1016/j.bmc.2011.12.057