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BY-NC-ND 3.0 license Open Access Published by De Gruyter Open Access March 1, 2004

Antiinflammatory, analgesic and kinase inhibition activities of some acridine derivatives

  • Sham Sondhi EMAIL logo , Gurudas Bhattacharjee , Rafid Jameel , Rakesh Shukla , Ram Raghubir , Olivier Lozach and Laurent Meijer
From the journal Open Chemistry

Abstract

9-Chloro-2,4-(un)substituted acridines (1) on condensation with sulpha- diazine, sulphathiazole, and sulphaacetamide gave condensation products 3a-h. 3-Aryl-4-phenyl-2-imino-4-thiazolines (4) on condensation with 9-chloro-2,4-(un)substituted acridines (1) gave condensation products 5a–5o. Both 3a–3h and 5a–5o were purified by crystallization or by chromatography. Structures assigned to 3a–3h and 5a–5o are supported by correct spectral data. Antiinflammatory and analgesic activity screening of 3a, 3e, 3f and 5a–5c, 5e, 5g, 5i, 5m, 5n were carried out using carrageenin induced paw oedema and phenyl quinone writhing assay. Some of the compounds exhibited interesting antiinflammatory or analgesic activities.

[1] V.K. Misra and S.C. Bahel: “Synthesis of thaiazolyl compounds as potential fungicides”, Journal of Indian Chemical Society, Vol. 61, (1984), pp. 916–918. Search in Google Scholar

[2] A. Srivastava, R.B. Pathak, S.C. Bahel: “Synthesis of antifungal N-acridin-5-yl, N′-α-aryloxy-butanoylhydrazines”, Journal of Indian Chemical Society, Vol. 62, (1985), pp. 486–487. Search in Google Scholar

[3] L. Ngadi, N.G. Bisri, A. Mahamoud, A.M. Galy, J.P. Galy, J.C. Soyfer, J. Barbe, M. Placidi: “Synthesis and antiparasitic activity of new 1-nitro, 1-amino and 1-acetamido-9 acridonones”, Arzeimittel Forsch, Vol. 43, (1993), pp. 480–483. Search in Google Scholar

[4] I.S. Shul’ga, A.K. Sukhomlinov, I.A. Goncharov, and E.M. Dikaya: “Synthesis and antimicrobial activity of some 4-nitro-aminoacridine derivatives”, Farm. Zh. (Kiev), Vol. 29, (1974), pp. 27–29. Search in Google Scholar

[5] N.A. Gaiukevich, G.S. Bashura, I.M. Pestsev, O.A. Pimenov and A.I. Pyatkop: “Antimicrobial activity of some acridine derivatives”, Farm. Zh. (Kiev), Vol. 28, (1973), pp. 50–54. Search in Google Scholar

[6] G.W. Gribble, G.D. Jaycox and M. Mosher: “Preparation of bis (9-aminoacridine) DNA intercalating agents having antitumor activity”, PCT Int. Appl. W.O. 9857956; Chem. Abstr., Vol. 130, (1999), 66397u. Search in Google Scholar

[7] T. Sugaya, Y. Mimura, Y. Shida, Y. Osawa, I. Matsukuma: “6H-Pyrazolo [4,5,1-de]acridin-6-ones as a novel class of antitumor agents. Synthesis and biological activity”, Journal of Medicinal Chemistry, Vol. 37, (1994), pp. 1028–1032. http://dx.doi.org/10.1021/jm00033a02010.1021/jm00033a020Search in Google Scholar

[8] M. Kimura, I. Okabayashi and A. Kato: “Acridine derivatives V [1]. Synthesis and P388 antitumor activity of novel 9-anilino-2,3-ethylenedioxyacridines”, J. Het. Chem., Vol. 30, (1993), pp. 1101–1104. http://dx.doi.org/10.1002/jhet.557030044610.1002/jhet.5570300446Search in Google Scholar

[9] S.G. Isaev, I.S. Shul’ga, A.V. Kaliman, N.E. Sheveleva and L.F. Silaeva: “Synthesis and biological activity of 9-arylamino acridine nitro derivatives”, Farm. Zh. (Kiev), Vol. 2, (1988), pp. 68–69. Search in Google Scholar

[10] I.B. Taraporewala and J.M. Kauffman: “Synthesis and structure activity relationships of anti-inflammatory 9,10-dihydro-9-oxo-2-acridinealkanoic acids and 4-(2-carboxyphenyl) aminobenzene alkanoic acids”, J. Pharm. Sci., Vol. 79, (1990), pp. 173–178. http://dx.doi.org/10.1002/jps.260079021910.1002/jps.2600790219Search in Google Scholar

[11] A.N. Gaidukevich, G.P. Kazakov, A.A. Kravchenko, L.A. Porokhnyak, V.V. Dinchuk: “Synthesis and biological activity of acridinyl-9-thioacetic acid and their derivatives”, Khim. Farm. Zh., Vol. 21, (1987), pp. 1067–1070; Chem. Abstr., Vol. 108, (1988), 68486s. Search in Google Scholar

[12] W.E. Bondinell, V.A. Reader and T.W.F. Ku: “Subistituted bisacridines and related compounds as CCR5 receptor ligands, antinflammatory agents and antiviral agents”, PCT Int. Appl. W.O. 9830218; Chem. Abstr., Vol. 129, (1998), 122582 u. Search in Google Scholar

[13] W.A. Denny, B.C. Baguley, B.F. Cain and M.J. Waring: “Antitumor acridines in molecular aspects of anticancer drug action”, E. Neidle and M.J. Waring (Ed.), Macmillan, London, (1983), pp. 1–34. Search in Google Scholar

[14] W.A. Denny, B.F. Cain, E.J. Atwell, C. Hansch, A. Pathananickal and A. Leo: “Potential antitumor agents. 36 Quantitative relationships between experimental antitumor activity, toxicity and structure for the general class of 9-anilinoacridine antitumor agents”, J. Med, Chem., Vol. 25, (1982), pp. 276–315. http://dx.doi.org/10.1021/jm00345a01510.1021/jm00345a015Search in Google Scholar

[15] B.C. Baguley, W.A. Denny, G.J. Atwell, G.J. Finlay, G.W. Rewcastle, S.J. Twigden and W.R. Wilson: “Synthesis, antitumor activity, and DNA binding properties of new derivatives of amsacrine, N-5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino)phenylamino]-4-acridinecarboxamide”, Cancer Res., Vol. 44, (1984), pp. 3245–3251. Search in Google Scholar

[16] S.M. Sondhi, M. Johar, S. Rajvanshi, S.G. Dastidar, R. Shukla, R. Raghubir and J.W. Lown: “Anticancer, anti-inflammatory, and analgesic activity evaluation of heterocyclic compouds synthesized by the reaction of 4-isothiocyanato-4-metylpentan-2-one with substituted o-phenylenediamines, o-diaminopyridine and (un) substituted o-diaminopyridines”, Australian Journal of Chemistry, Vol. 54, (2001), pp. 69–74. http://dx.doi.org/10.1071/CH0014110.1071/CH00141Search in Google Scholar

[17] S.M. Sondhi, M. Johar, R. Shukla, R. Raghubir, N. Bharti and A. Azam: “Synthesis, antiinfalmmatory, analgesic and antiamoebic activity evaluation of some Pyrimidobenizimidazole and pyrimidopyridoimidazole derivatives”, Australian Journal of Chemistry, Vol. 54, (2001), pp. 461–467. http://dx.doi.org/10.1071/CH0105510.1071/CH01055Search in Google Scholar

[18] S.M. Sondhi, N. Singhal, M. Johar, B.S. Narayan Reddy and J.W. Lown: “Heterocyclic compounds as inflammation inhibitors”, a review., Curr. Med. Chem., Vol. 9, (2002), pp. 1045–1074. http://dx.doi.org/10.2174/092986702460667810.2174/0929867024606678Search in Google Scholar

[19] S.M. Sondhi, S. Rajvanshi, M. Johar, N. Bharti, A. Azam and A.K. Singh: “Antiinflammatory, analgesic and antiamoebic activityevaluation of pyrimido[1,6-a]benzimidazole derivatives synthesized by the reaction of ketoisothiocyanates with mono and diamines”, Eur. J. Med. Chem., Vol. 37, (2002), pp. 835–843. http://dx.doi.org/10.1016/S0223-5234(02)01403-410.1016/S0223-5234(02)01403-4Search in Google Scholar

[20] S.M. Sondhi, N. Singhal, R.P. Verma, S.K. Arora and S.G. Dastidar: “Synthesis of hemin and porphyrin derivatives and their evaluation for anticancer activities”, Indian Journal of Chemistry, Sec. B, Vol. 40, (2001), pp. 113–119. Search in Google Scholar

[21] S.M. Sondhi, S. Rajvanshi, M. Johar, S.G. Dastidar: “Synthesis and anticancer activity evaluation of some hemin and hematoporphyrin derivatives”, Indian Journal of Chemistry, Sec. B, Vol. 41, (2002), pp. 388–393. Search in Google Scholar

[22] S.M. Sondhi, M. Johar, N. Singh and S.G. Dastidar: “Synthesis of bis coupled hemin-thiazoline derivatives and their anticancertivity evaluation”, Indian Journal of Chemistry Sec. B, (In Press). Search in Google Scholar

[23] C.F.H. Allen and G.H.W. Mcbee: “Acridone”, Org. Synthesis Coll., Vol. 2, (1959), pp. 15–17. Search in Google Scholar

[24] A. Albert and B. Ritiche: “9-Aminoacridine”, Org. Synthesis Coll., Vol. 3, (1960), pp. 53–56. Search in Google Scholar

[25] M.P. Mahajan, S.K. Vasudeva and N.K. Ralhan: “Synthesis of 2-Iminothiazolines”, Indian Journal of Chemistry, Vol. 10, (1972), pp. 318–319. Search in Google Scholar

[26] C.A. Winter, E.A. Risley and G.W. Nuss: “Carrageenin induced edema in hind paw of the rat as an assay for anti-inflammatory drugs”, Proc. Soc. Exp. Biol. Med., Vol. 111, (1962), pp. 544–547. Search in Google Scholar

[27] P.P. Singh, A.Y. Junnarkar, C.S. Rao, R.K. Verma and D.R. Shridhar: “Acetic acid phenylquinone writhing test: A critical study in mice”, Meth. Find. Exptl. Clinc. Pharmacol., Vol. 5, (1983), pp. 601–606. Search in Google Scholar

[28] A. Primot, B. Baratte, M. Gompel, A. Borgan, et. al: “Purification of GSK-3 by affinity chromatography on immobilized axin”, Protein Expression Purification, Vol. 20, (2000), pp. 394–404. http://dx.doi.org/10.1006/prep.2000.132110.1006/prep.2000.1321Search in Google Scholar PubMed

[29] S. Lecler, M. Garnier, R. Hoessel, D. Marko, J.A. Bibb, et. al: “Indirubins inhibit glycogen synthase Kinase-3β and CDK-5/p 25, two kinases involved in abnormal tau phosphorylation in Alzheimer’s disease-A property common to most CDK inhibitors?”, J. Biol. Chem., Vol. 276, (2001), pp. 251–260. http://dx.doi.org/10.1074/jbc.M00246620010.1074/jbc.M002466200Search in Google Scholar PubMed

[30] M. Leost, C. Schultz, A. Link, Y.Z. Wu, J. Biernat, E.M. Mandelkow: “Paullones are potent inhibitors of glycogen synthase kinase—3β and cyclin-dependent 5/p25”, European Journal of Biochemistry, Vol. 267, (2000), pp. 5983–5994. http://dx.doi.org/10.1046/j.1432-1327.2000.01673.x10.1046/j.1432-1327.2000.01673.xSearch in Google Scholar PubMed

Published Online: 2004-3-1
Published in Print: 2004-3-1

© 2004 Versita Warsaw

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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