European Journal of Chemistry

Novel antimicrobial and anti-acetylcholinesterase dihydroisoxazoles from (R)-limonene



Main Article Content

Enis Ben Bnina
Anis Romdhane
Majda Daami-Remadi
Hichem Ben Jannet

Abstract

We report herein the convenient procedures for the efficient and easy synthesis, and the antimicrobial and the anti-acetylcholinesterase evaluation of two new series of (R)-limonene derivatives. A substantial modification aimed at targeting to discover novel structures with a better antimicrobial and anti-acetylcholinesterase (anti-AChE) activities. The condensation of (R)-limonene (1) with various arylnitrile oxides led, via the 1,3-dipolar cycloaddition reaction, conducted with complete region-specificity, to a series of new limonene-dihydroisoxazoles, 2a-h. On the other hand, N-alkylation of the previously prepared limonene-lactam derivative (3) yielded the corresponding dipolarophile (4), which affords by condensation with arylnitrile oxides the expected new dihydroisoxazoles, 5a-h. The target compounds were completely characterized by 1H NMR, 13C NMR and MS. All the synthesized heterocyclic compounds were tested for their antimicrobial and anti-acetylcholinesterase activities. The dihydroisoxazoles 2a (IZ = 13.25 mm, cc = 1 mg/mL) and 5b (IZ = 13.75 mm, cc = 1 mg/mL) exhibited the highest antifungal activity. The greatest anti-acetylcolinesterase activity was exhibited by 2f (IC50 = 82±3 µg/mL) and by 5a (IC50 = 99±1 µg/mL).


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Bnina, E. B.; Romdhane, A.; Daami-Remadi, M.; Jannet, H. B. Novel Antimicrobial and Anti-Acetylcholinesterase Dihydroisoxazoles from (R)-Limonene. Eur. J. Chem. 2015, 6, 21-30.

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References

[1]. Guenther, A.; Geron, C.; Pierce, T.; Brian, L.; Harley, P.; Fall, R. Atmos. Environ. 2000, 234, 2205-2230.
http://dx.doi.org/10.1016/S1352-2310(99)00465-3

[2]. Crowell, P. L. J. Nutr. 1999, 129, 775S-778S.

[3]. Singh, P.; Shukla, R.; Prakash, B.; Kumar, A.; Singh, S.; Mishra, P. K.; Dubey, N. K. Food Chem. Toxicol. 2010, 48, 1734-1740.
http://dx.doi.org/10.1016/j.fct.2010.04.001

[4]. Ferrarini, S. R.; Duarte, M. O.; DaRosa, R. G.; Rolim, V.; EiflerLima, V. L.; VonPose, G.; Ribeiro, V. L. S. Vet. Parasitol. 2008, 157, 149-153.
http://dx.doi.org/10.1016/j.vetpar.2008.07.006

[5]. Elson, C. E.; Maltzman, T. H.; Boston, J. L.; Tanner, M. A.; Gould, M. N. Carcinogenesis 1988, 9, 331-332.
http://dx.doi.org/10.1093/carcin/9.2.331

[6]. Elegbede, J. A.; Maltzman, T. H.; Verma, A. K.; Tanner, M. A.; Elson, C. E.; Gould, M. N. Carcinogenesis 1999, 7, 2047-2049.
http://dx.doi.org/10.1093/carcin/7.12.2047

[7]. Dietrich, D. R.; Swenberg, J. A. Cancer. Re.s 1991, 51, 3512-3521.

[8]. Wattenberg, L. W.; Coccia, J. B. Carcinogenesis 1991, 12, 115-117.
http://dx.doi.org/10.1093/carcin/12.1.115

[9]. Nakaizumi, A.; Baba, M.; Uehara, H.; Iishi, H.; Tatsuta, M. Cancer Lett. 1997, 117, 99-103.
http://dx.doi.org/10.1016/S0304-3835(97)00207-3

[10]. Chen, J.; Lu, M.; Jing, Y.; Dong, J. J. Bioorg. Med. Chem. 2006, 14, 6539-6547.
http://dx.doi.org/10.1016/j.bmc.2006.06.013

[11]. Maltzman, T. H.; Hurt, L. M.; Elson, C. E.; Tanner, M. A.; Gould, M. N. Carcinogenesis 1989, 10, 781-783.
http://dx.doi.org/10.1093/carcin/10.4.781

[12]. Yang, Y. Q.; Zhao, G. Chem. Eur. J. 2008, 14, 10888-10891.
http://dx.doi.org/10.1002/chem.200801749

[13]. Cimarelli, C.; Fratoni, D.; Palmieri, G. Tetrahedron-Asymmetr. 2009, 20, 2234-2239.
http://dx.doi.org/10.1016/j.tetasy.2009.08.012

[14]. Hensen, K.; Mahaim, C.; Holderich, W. F. Appl. Catal. A-Gen. 1997, 149, 311-329.
http://dx.doi.org/10.1016/S0926-860X(96)00273-6

[15]. Chang, S. S.; Peterson, R. J. J. Food Sci. 1977, 42, 298-305.
http://dx.doi.org/10.1111/j.1365-2621.1977.tb01486.x

[16]. Midori, A. A.; Toshio, S.; Takayoshi, A.; Hiroaki, S. Yuki Gosei Kagaku Kyokaishi 2004, 62, 59-69.
http://dx.doi.org/10.5059/yukigoseikyokaishi.62.59

[17]. Quadrelli, P.; Scrocchi, R.; Caramella, P.; Rescifina, A.; Piperno, P. Tetrahedron 2004, 60, 3643-3651.
http://dx.doi.org/10.1016/j.tet.2004.02.057

[18]. Lam, P. Y. S.; Adams, J. J.; Clark, C. G.; Calhoun, W. J.; Luettgen, J. M.; Knabb, R. M.; Wexler, R. R. Bioorg. Med. Chem. Lett. 2003, 13, 1795-99.
http://dx.doi.org/10.1016/S0960-894X(03)00130-6

[19]. Kai, H.; Mastsumoto, H.; Hattori, N.; Takase, A.; Fujiwara, T.; Sugimoto, H. Bioorg. Med. Chem. Lett. 2001, 11, 1997-2000.
http://dx.doi.org/10.1016/S0960-894X(01)00362-6

[20]. Tangallapally, R. P.; Sun, D.; Rakesh; Budha, N.; Lee, R. E.; Lenaerts, A. J.; Meibohm, B.; Lee, R. E. Bioorg. Med. Chem. Lett. 2007, 17, 6638-6642.
http://dx.doi.org/10.1016/j.bmcl.2007.09.048

[21]. Jadhav, S. B.; Shastri; R. A.; Gaikwad, K. V.; Gaikwad, S. V. E-J. Chem. 2009, 6(S1), S183-S188.

[22]. Jayashankara, B.; LokanathaRai, K. M. Arkivoc 2008, 11, 75-85.
http://dx.doi.org/10.3998/ark.5550190.0009.b07

[23]. Prasad, Y. R.; Ravikumar, P.; Ramesh, B. Int. J. Chem. Sci. 2007, 5, 542-548.

[24]. Amici, M. D.; Conti, P.; Vistoli, G.; Carrea, G.; Ottolina, G.; DeMicheli, C. Med. Chem. Res. 2001, 10, 615-633.

[25]. Park, K. K.; Ko, D. H.; You, Z.; Khan, M. O.; Lee, H. J. Steroids 2006, 71, 183-188.
http://dx.doi.org/10.1016/j.steroids.2005.10.003

[26]. Hwang, I. T.; Kim, H. R.; Jeon, J. D.; Hong, K. S.; Song, J. H.; Cho, K. Y. J. Agric. Food Chem. 2005, 53, 8639-8643.
http://dx.doi.org/10.1021/jf051284f

[27]. Li, X. F.; Feng, Y. Q.; Xu, M. Acta. Crystallogr. E 2003, 59, O675-O676.
http://dx.doi.org/10.1107/S1600536803008134

[28]. Pedro, A. C.; Volker, J.; Albrecht, L.; Rodolfo, D. B. Tetrahedron 2003, 44, 1071-1074.
http://dx.doi.org/10.1016/S0040-4039(02)02665-5

[29]. Nair, V.; Suja, T. D. Tetrahedron 2007, 63, 12247-12275.
http://dx.doi.org/10.1016/j.tet.2007.09.065

[30]. Pellissier, H. Tetrahedron 2007, 63, 3235-3285.
http://dx.doi.org/10.1016/j.tet.2007.01.009

[31]. Feddaoui, A.; AitItto, M. Y.; AitAli, M.; Hasnoui, A.; Riahi, A. Synth. Commun. 2006, 36, 3617-3624.

[32]. Clemett, D.; Markham, A. Drugs 2000, 59, 815-827.
http://dx.doi.org/10.2165/00003495-200059040-00007

[33]. GarciaMoreno, M. I.; DiazPérez, P.; Ortiz, M. C.; Garcia, F. J. M. J. Org. Chem. 2003, 68, 8890-8901.

[34]. Dighade, S. R.; Patil, S. D.; Chincholkar, M. M.; Dighade, N. R. Asian J. Chem. 2003, 15, 450-454.

[35]. Barbachyn, M. R.; Cleek, G. J.; Dolak, L. A.; Garmon, S. A.; Morris, J.; Seest, E. P.; Thomas, R. C.; Toops, D. S.; Watt, W.; Wishka, D. G.; Ford, C. W.; Zurenko, G. E.; Hamel, J. C.; Schaadt, R. D.; Stapert, D.; Yagi, B. H.; Adams, W. J.; Friis, J. M.; Slatter, J. P.; Oien, N. L.; Zaya, M. J.; Wienkers, L. C.; Wynalda, M; A. J. Med. Chem. 2003, 46, 284-302.
http://dx.doi.org/10.1021/jm020248u

[36]. Basappa, Sadashiva, M. P.; Mantelingu, K.; Nanjunda, S. S.; Rangappa, K. S. Bioorg. Med. Chem 2003, 11, 4539-4544.
http://dx.doi.org/10.1016/j.bmc.2003.08.007

[37]. Gyonfalvi, S.; Szakonyi; Z.; Fulop, F. Tetrahedron-Asymmetr. 2003, 14, 3965-3972.

[38]. Woznica, M.; Butkiewicz, A.; Grzywacz, A.; Kowalska, P.; Masnyk, M.; Michalak, K.; Luboradzki, R.; Furche, F.; Kruse, H.; Grimme, S.; frelek, J. J. Org. Chem. 2011, 76, 3306-3319.

[39]. Alcontres, G. S.; Caristi, C.; Ferlazzo, A.; Gattuso, M. J. Chem. Soc. Perkin Trans. 1976, 1, 1694-1696.
http://dx.doi.org/10.1039/p19760001694

[40]. Harhash, A. H.; Elnagdi, M. H.; Kassab, N. A. L.; Negm, A. M. J. Chem. Eng. Data 1975, 20, 120-122.
http://dx.doi.org/10.1021/je60064a018

[41]. Fale, P. L.; Borges, C.; AmorimMadeira, P. J.; Ascensao, L.; Araujo, M. E. M.; Florencio, M. H.; Serralheiro, M. L. M. Food Chem. 2009, 114, 798-805.

[42]. Orhan, G.; Orhan, I.; Sener, B. Lett. Drug. Des. Discov. 2003, 3, 268-274.
http://dx.doi.org/10.2174/157018006776743215

[43]. Howes, M. J.; Houghton, P. J. Pharmacol. Biochem. Behav. 2003, 75, 513-527.
http://dx.doi.org/10.1016/S0091-3057(03)00128-X

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