In-vivo Anticonvulsant and In-vitro Antitubercular Activity of methyl Indole Derivative of some 6-aryl-4, 5-Dihydropyridazin-3(2H)-ones and their Expected Anticonvulsant Mechanisms Anticonvulsant & Anti-TB activity of 6-aryl-dropyridazin-3(2H)-nes
Iranian Journal of Pharmaceutical Sciences,
Vol. 9 Núm. 1 (2013),
6 February 2024
,
Página 67-80
https://doi.org/10.22037/ijps.v9.40920
Resumen
Methyl indole derivative of some 6-aryl-4,5-dihydropyridazin-3(2H)-ones (3a-e) were synthesized by Mannich reaction and evaluated as anticonvulsant against MES (50mA, for 2sec), INH (250mg/kg), scPTZ (80mg/kg) and STR (3mg/kg) induced convulsion methods at 50 mg/kg dose level. All compounds 3a-e were also evaluated as antitubercular agent against M. tuberculosis H37Rv by MABA method. All compounds 3a-e showed anticonvulsant activities against MES, INH and scPTZ-induced convulsions methods but no compounds were active against STR-induced method. Compound 3b, compound 3d and 3e showed highest protection against MES, INH and scPTZ-induced convulsion models respectively. Compound 3d showed highest antitubercular activity, with 12.5μg/ml MIC value. Previous data reported that the pyridazinones are the important biological compounds which possess almost all types of biological activities. Due to this reason, we synthesized some pyridazinone compounds and characterized them by spectral analysis. Results indicated that title compounds showed moderate to good anticonvulsant activities but less antitubercular activity.
- Anticonvulsant
- antitubercular
- biological active
- heterocyclic
- pyridazinone
- synthetic
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[2] Zhou et al. studies of pyridazinone derivatives as novel glucan synthase inhibitors. Bioorg Med Chem Lett, 2011, 21(10): 2890-2893.
[3] Xu et al. Synthesis and herbicidal activity of novel alpha, alpha, alpha-trifluoro-m-tolyl pyridazinone derivatives. Pest. Manag. Sci, 2006, 62(6): 522-530.
[4] Husain A, Drabu S, Kumar N, Alam MM, Ahmad A. Synthesis and biological evaluation of some new pyridazinone derivatives. J En Inhib Med Chem, 2011, 26(5): 742-748.
[5] Faidallah HM, Khan KA, Makki MSI. Synthesis and Biological Evaluation of New Fused Isoxazolo[4,5-d] Pyridazine Derivatives. J. Chinese Chem. Soc, 2011, 58: 191-198.
[6] Cao S, Qian X, Song G, Chai B, Jiang Z. Synthesis and Antifeedant Activity of New Oxadiazolyl 3(2H)-Pyridazinones. J. Agric. Food Chem., 2003, 51(1): 152-155.
[7] Huang Q, Kong Y, Liu M, Feng J, Liu Y. Effect of oxadiazolyl 3(2H)-pyridazinone on the larval growth and digestive physiology of the armyworm, Pseudaletia separate. J Insect Sci, 2008, 8: 1577-1580.
[8] Dogruer DS, Sahin MF, Unlu S, Shigeru I. Studies on some 3(2H)-pyridazinone derivatives with antinociceptive activity. Arch. Pharm., (Weinheim), 2000, 333; 79-86.
[9] Gokce M, Utku S, Kupeli E. Synthesis and analgesic and anti-inflammatory activities 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted/nonsubstitutedbenzal)hydrazone derivatives. Eur. J. Med. Chem, 2009, 44(9): 3760-3764.
[10] Piaz VD, Giovannoni MP, Ciciani G, Barlocco D, Giardina G, Petrone G, Clarke GD. 4,5-Functionalized-6-phenyl-3(2H)-pyridazinones:synthesis and evaluation of antinociceptive activity, Eur. J. Med. Chem, 1996; 31: 65-70.
[11] Rubat C, Coudert P, Tronche P, Bastide J, Bastide P, Privat AM. Synthesis and pharmacological evaluation of N-substituted 4, 6-diaryl-3-pyridazinones as analgesic, antiinflammatory and antipyretic agents. Chem. Pharm. Bull., (Tokyo), 1989, 37(10): 2832-2835.
[12] Sukuroglu M, Ergun BC, Unlu S, Sahin MF, Kupeli E, Yesilada E, Banoglu E. Synthesis, analgesic, and anti-inflammatory activities of [6-(3,5-di methyl-4-chloropyrazole-1-yl)-3(2H)-pyridazinon-2-yl]acetamides. Arch. Pharm. Res, 2005, 28(5); 509-517.
[13] Asif M. General study of pyridazine compounds against cyclooxygenase enzyme and their relation with analgesic, anti-inflammatory and anti-arthritic activities. Chronicles of Young Scientists, 2010, 1(3): 3-9.
[14] Asif M, Anita S, Lakshmayya, Siddiqui AA, Husain A. Anti-inflammatory andantinociceptive activities of 6-phenyl (3’-imino-benzylidene)-4-benzylidene-2,3,5-trihydro-3-(2H)-pyridazin-3-one compounds, Acta Pharm Sciencia, 2011, 53: 563-575.
[15] Edith G, Ales K, Winfried W and Marija K. Synthesis and Structure Investigations of Potential Sedative and Anticonvulsant Hydroxy- and Acetoxy-N-(3-oxobutyl)-pyrido[2,3-d] pyridazinones. Monatshefte für Chemie, 2002, 133(9): 1177-1185.
[16] Gong Y, Barbay JK, Dyatkin AB, Miskowski TA, Kimball ES, Prouty SM, Fisher MC, Santulli RJ, Schneider CR, Wallace NH, Ballentine SA, Hageman WE, Masucci JA, Maryanoff BE, Damiano BP, Andrade-Gordon P, Hlasta DJ, Hornby PJ, He W. Synthesis and biological evaluation of novel pyridazinone-based alpha4 integrin receptor antagonists. J. Med. Chem., 2006, 49(11): 3402-3411.
[17] Jeremy RG, Graziano V, Hugh RC, Kenneth NM, Robin DA. Theoretical studies on the free-radical bromination of methyl-pyridazines in the synthesis of novel heterocyclic analogues of neurotransmitters. J. Mol. Str., (Theochem), 1996, 368: 235-243.
[18] Abouzid K, Hakeem MA, Khalil O, Maklad Y. Pyridazinone derivatives: design, synthesis, and in vitro vasorelaxant activity. Bioorg. Med. Chem., 2008, 16: 382–389.
[19] Bansal R, Kumar D, Carron R, de la Calle C. Synthesis and vasodilatory activity of some amide derivatives of 6-(4-carboxymethyloxyphenyl)-4,5-dihydro-3(2H)-pyridazinone. Eur J Med Chem. 2009, 44(11): 4441-4447.
[20] Cherng SC, Huang WH, Shiau CY, Lee AR, Chou TC. Mechanisms of antiplatelet activity of PC-09, a newly synthesized pyridazinone derivative. Eur. J. Pharmacol., 2006, (1-2); 32-37.
[21] Costas T, Besada P, Piras A, Acevedo L, Yañez M, Orallo F, Laguna R, Teran C. New pyridazinone derivatives with vasorelaxant and platelet antiaggregatory activities. Bioorg. & Med. Chem. letters. 2010, 20(22): 6624-6627.
[22] Kumar D, Carron R, La Calle CD, Jindal DP, Bansal R. Synthesis and evaluation of 2-substituted-6-phenyl-4,5-dihydropyridazin-3(2H)-ones as potent inodilators. Acta Pharm., 2008, 58(4): 393-405.
[23] Siddiqui AA, Mishra R, Shaharyara M, Husain A, Rashid M, Pal P. Triazole incorporated pyridazinones as a new class of antihypertensive agents: Design, synthesis and in vivo screening. Bioorg Med Chem Lett, 2011, 21: 1023–1026.
[24] Allerton CM, Andrews MD, Blagg J, Ellis D, Evrard E, Green MP, Liu KK, McMurray G, Ralph M, Sanderson V, Ward R, Watson L. Design and synthesis of pyridazinone-based 5-HT(2C) agonists. Bioorg. Med. Chem. Lett., 2009, 1(19); 5791-5.
[25] Chintakunta VK, Akella V, Vedula MS, Mamnoor PK, Mishra P, Casturi SR, Vangoori A, Rajagopalan R. 3-O-substituted benzyl pyridazinone derivatives as COX inhibitors. Eur. J. Med. Chem., 2002, 37: 339-347.
[26] Coudert P, Rubat C, Tronche P, Bastide P, Bastide J. Synthesis and antisecretory and anti-ulcer activity of new 4,6-diarylpyridazinones. Pharm. Acta Helv, 1989, 64(5-6): 159-162.
[27] Derson V, Ward R, Watson L. Design and synthesis of pyridazinone-based 5-HT(2C) agonists. Bioorg. Med. Chem. Lett., 2009, 19(19): 5791-5795.
[28] Malinka W, Redzicka A, Lozach, O. New derivatives of pyrrolo[3,4-d] pyridazinone and their anticancer effects. Farmaco, 2004, 59(6): 457-462.
[29] Yalamanchili P, Wexler E, Hayes M, Yu M, Bozek J, Kagan M, Radeke HS, Azure M, Purohit A, Casebier DS, Robinson SP. Mechanism of uptake and retention of F-18 BMS-747158-02 in cardiomyocytes: a novel PET myocardial imaging agent. J. Nucl. Cardiol., 2007, 14(6): 782-8.
[30] Youssef ASA, Marzouk MI, Madkour HMF, El-Soll MA, El-Hashash M. A. Synthesis of some heterocyclic systems of anticipated biological activities via 6-aryl-4-pyrazol-1-yl-pyridazin-3-one. Can. J. Chem., 2005, 83(3): 251–259.
[31] Rathish IG, Javed K, Bano S, Ahmad S, Alam MS, Pillai KK. Synthesis and blood glucose lowering effect of novel pyridazinone substituted benzenesulfonylurea derivatives. Eur. J. Med. Chem., 2009, 44(6): 2673-8.
[32] Asif M. Some Recent Approaches of Biologically Active Substituted Pyridazine and Phthalazine Drugs. Curr Med Chem. 2012, 19(18): 2984-2991.
[33] Asif M. Study of clinically used and recently developed antimycobacterial agents. Orient Pharm Exp Med. 2012, 12: 15–34.
[34] Asif M. A Review of Antimycobacterial Drugs in Development. Mini Rev Med Chem. 2012, 12(13): 1404-1418.
[35] Hallot A, Brodin R, Merlier J, Brochard J, Chambon JP, Biziere K. Synthesis and activity of 6-aryl-3-(hydroxypolymethyleneamino) pyridazines in animal models of epilepsy. J Med Chem. 1986, 29(3): 369-75.
[36] Asif M. Recent Approaches toward Anticonvulsant Activity of Pyridazine Compounds. Open J Org Chem, 2013, 1(2):11-21.
[37] Oya Ü, Ayla B, Cenk A, Berna TM, Zafer G. (2004) Synthesis and Evaluation of the Anticonvulsant Activities of Some 5-(4-substitutedbenzylidene)-6-methyl-4,5-dihydro pyridazine-3(2H)-ones. FABAD J. Pharm. Sci., 2004, 29: 185-194.
[38] Deniz SD, Tijen O, Semiha O, Selda O, Fethi MS. Synthesis and Antimicrobial Activity of Some 3(2H)-Pyridazinone and 1(2H)-Phthalazinone Derivatives. Turk. J. Chem. 2008, 32, 469-479.
[39] Islam M., Siddiqui AA, Rajesh R. Synthesis, Antitubercular, Antifungal and Antibacterial Activities of 6-Substituted Phenyl-2-(3’-Substituted Phenyl Pyridazin-6’-yl)-2,3,4,5-Tetrahydropyridazin-3-one. Acta Pol Pharm, 2008, 65 (3): 353-362.
[40] Islam M, Siddiqui, AA, Rajesh R. Synthesis, antitubercular, antifungal and antibacterial activities of 6-substituted phenyl-2-(3’-Substituted Phenyl Pyridazin-6’-yl)-2,3,4,5-tetrahydropyridazin-3-One. Acta Pol. Pharm., 2008, 65(4), 441-447.
[41] Perio A, Chambon JP, Calassi R, Heaulme M, Biziere K. Evaluation of two anticonvulsant amino-pyridazine derivatives in the conflict test in rats. J Pharmacol Exp Ther. 1986, 239(2): 542-7.
[42] Siddiqui AA, Abdullah MM, Arora M, Islam M. Ahmad SR. Synthesis of Novel Pyridazinones Possessing Anticonvulsant Activity. Indian drugs. 2006, 43(10): 790-794.
[43] Sivakumar R, Anbalagan N, Gunasekaran V, Leonard JT. Synthesis and anticonvulsant activity of novel 1-substituted-1,2-dihydro-pyridazine-3,6-diones. Biol Pharm Bull., 2003, 26(10): 1407-1411.
[44] Xu P, Wang SY, Chen Y, Liu WQ, Tao C. Studies on synthesis, anticonvulsant activity and the structure--activity relationships of 6-(substituted phenyl)-3 (2H) pyridazinones. Yao Xue Xue Bao. 1991, 26(9): 656-660.
[45] Siddiqui AA, Mishra R, Shaharyar M. Synthesis, characterization and antihypertensive activity of pyridazinone derivatives. Eur. J. Med. Chem., 2010, 45 (6): 2283-2290.
[46] Kulkarni SK. Handbook of experimental pharmacology 3rd edition vallabh publication New Delhi, 1999, 131-133.
[47] Lourenco MCS, deSouza MVN, Pinheiro AC, Ferreira ML, Goncalves RB, Nogneira TCM, Peralta MA. Evaluation of antitubercular activity of nicotinic and isoniazid analogues. Arkivoc. 2007, (xv):181-191.
[48] Meenakshi D, Pravin S, Ashok B, Kapil J, Rahul D, Pramod S. Synthesis and evaluation of phenytoin derivatives as anticonvulsant agents. Turk J Chem. 2009, 33, 1-7.
[49] Sivakumar S, Surendra N. P, James P. S, Suthakar G. Anticonvulsant and Sedative-Hypnotic Activities of N-Acetyl / Methyl Isatin Derivatives. Sci Pharm. 2008; 76: 621-636.
[50] Xu P, Wang SY, Liu WQ. Studies on synthesis and anticonvulsant activity of 3-GABA derivatives of 6-(substituted-phenyl) pyridazines. Yao Xue Xue Bao. 1991, 26(9):650-655.
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