Document Type : Original Article

Authors

1 Analytical, Structural and Materials Chemistry Laboratory, Department of Chemistry, Faculty of Science, University of Douala, P.O. Box 24157, Douala, Cameroon

2 Department of Pharmaceutical Sciences, Faculty of Medicine and Pharmaceutical Sciences, University of Douala, P.O. Box 24157, Douala, Cameroon

Abstract

A new pyrrolidinyl-piperazine alkaloid derivative named 2-(7’-methylhexyloxy)furan-5’-yl)-6- (pyrrolidin-7-yl)piperazine (1), along with five known compounds were isolated from methanolic extract of the roots of Oxyanthus speciosus DC. (Rubiaceae). The structure of this new alkaloid was elucidated on the basis of the relevant NMR and MS analyses. Compound (1) possesses potent in vitro anti-inflammatory activity by protein denaturation assay with an IC50 value of 1.930 ± 0.9123 µg/mL. The obtained results indicated that the crude methanolic extract of O. speciosus DC. roots and its isolated pyrrolidinyl-piperazine alkaloid have potentials for further development as an effective and natural anti-inflammatory agents.

Graphical Abstract

A new pyrrolidinyl-piperazine alkaloid derivative from Oxyanthus speciosus DC. (Rubiaceae)

Keywords

Adjanohoun, E.J., Ahyi, A.M.R., Ake, A.L., Baniakina, J., Chinon, P., Cusset, G., Doulou, V., Enzanza, A., Eymé, J., Goudoté, E., Keita, A., Mbemba, C., Mollet, J., Moutsaboté, J., Mpati, J., Sita, P., 1988. Contribution aux Etudes Ethnobotaniques et Floristiques en République Populaire du Congo. A.CC.T., Paris 605-606.
Aké, A.L., Abeye, J., Guinko, S., Riguet, R., Bangavou, X., 1985. Médecine traditionnelle et pharmacopée-Contribution aux études ethnobotaniques et floristiques en République Centrafricaine. A.C.C.T. Paris, France. 140 pp.
Aro, A.O., Dzoyem, J.P., Hlokwe, T.M., Madoroba, E., Eloff, J.N., Mcgaw, L.J., 2015. Some south african rubiaceae tree leaf extracts have antimycobacterial activity against pathogenic and non-pathogenic Mycobacterium species. Phytother. Res. 10, 1004-1010.
Aro, A.O., Dzoyem, J.P., Goddard, A., Fonteh, P., Kayoka-Kabongo, P.N., McGaw, L.J., 2019b. In vitro Antimycobacterial, apoptosis-inducing potential, and immunomodulatory activity of some Rubiaceae species. Front. Pharmacol. 10(185), 1-13.
Aro, A.O., Dzoyem, J.P., Awouafack, M.D., Selepe, M.A., Eloff, J.N., McGaw, L.J.A., 2019a. Fractions and isolated compounds from Oxyanthus speciosus subsp. stenocarpus (Rubiaceae) have promising antimycobacterial and intracellular activity. BMC Complement. Altern. Med. 19(108), 1-11.
Burkill, H.M., 1997. The Useful Plants of West Tropical Africa. 2nd Edition. Vol. 4, Families M-R. Royal Botanic Gardens, Kew, Richmond, United Kingdom.
Bouquet, A., 1969. Féticheurs et Médecine Traditionnelle du Congo (Brazzaville). Travaux et Documents de l’ORSTOM, Paris 36, 128.
Eder, B., Walmir, S.G., Lidilhone, H., Tieppo, C., Fernanda, R.G., 2008. Bioactive pentacyclic triterpenes from the stems of Combretum laxum. Molecules 13, 2717-2728.
Esposito, F., Sanna, C., Vecchio, C.D., Cannas, V., Venditti, A., Corona, A., Bianco, A., Serrilli, A.M., Guarcini, L., Parolin, C., Ballero, M., Tramontano, E., 2013. Hypericum hircinum L. components as new single-molecule inhibitors of both HIV-1 reverse transcriptase-associated DNA polymerase and ribonuclease H activities. Pathog. Dis. 68(3), 116-124.
Kokwaro, J.O., 1993. Medicinal Plants of East Africa. 2nd Ed. Kenya Literature Bureau, Nairobi, Kenya. 401 pp.
Liu, J., Xu, J., Zhao, J.X., Gao, Y.W., Zhang, Z.S., Guo, Q.Y., 2010. A new heterocyclic compound from Cyathula officinalis Kuan. Chin. Chem. Lett. 21, 70-72.
Mamat, C., Pretze, M., Gott, M., Köckerling, M., 2016. Synthesis, dynamic NMR characterization and XRD studies of novel N,N´-substituted piperazines for bioorthogonal labeling. Beilstein J. Org. Chem. 12, 2478-2489.
Marcos, P., Luciene, R.B., Abhinay, S., Myna, N., Amanda, D., Claudio, V.J., Celia, R.S.G., Vanderlan, S.B., 2014. Antimalarial activity of piperidine alkaloids from Senna spectabilis and semisynthetic derivatives. J. Braz. Chem. Soc. 25(10), 1900-1906.
Mikhova, B., Spassov, S.L., Popandova, K., Dryanska, V., Ivanov, C., Duddeck, H., Kaiser, M., 1987. NMR spectra and stereochemistry of some 2,3,4,5-tetrasubstituted pyrrolidines. J. Mol. Struct. 161, 1987, 231-235.
Mitsuo, M., Kimio, Y., Yukio, I., Hiromu, K., 1998. Insecticidal alkaloids against Drosophila melanogaster from Nuphar japonicum DC. J. Agric. Food. Chem. 46, 1059-1063.
Nahrstedt, A., Rockenbach, J., Wray, V., 1995. Phenylpropanoid glycosides, a furanone glucoside and lgeniposidic acid from members of the Rubiaceae. Phytochemistry39(2), 375-378.
Neoh, B., Rahayu, U., Nordin, H., Tai, Y.C., Tu, Y.L., Mawardi R., Aspollah, S., 2010. Chemical constituents from two weed species of Spermacoce (Rubiaceae). Malaysian J. Anal. Sci. 14, 6-11.
Neuwinger, H.D., 2000. African Traditional Medicine: A Dictionary of Plant Use and Applications. Medpharm Scientific, Stuttgart, Germany. 589 pp.
Nzedong, T.I.B., Ngnokam, D., Tapondjou, A.L., Harakat, D., Voutquenne, L., 2010. Cycloartane glycosides from leaves of Oxyanthus pallidus. Phytochemistry 71, 2182-2186.
Nzedong, T.I.B., Ngnokam, D., Tapondjou, L.A., Harakat, D., Voutquenne, L., 2012. Isolation and caracterisation of sodium monocarboxylate ixoside salt from the stem bark of Oxyanthus pallidus. Int. J. Biol. Chem. Sci. 6(6), 7007-7012.
Olajide, O.O., Okwute, S.K., 2019. Stigmasterol and stigmasterol glycoside: Isolated compounds from Tetrapleura tetraptera extracts. J. Biochem. Int. 6(1), 21-48.
Rajakumar, P., Thirunarayanan, A., Raja, S., 2014. Synthesis and antibacterial activity of novel N-methyl pyrrolidine dendrimers via [3+2] cycloaddition. Proc. Natl. Acad. Sci. India Sect. A Phys. Sci. 84, 371-379.
Raponda-Walker, A., Sillans, R., 1961. Les plantes utiles du Gabon. Paul Lechevalier, Paris, France. 614 pp.
Regnier, G.L., Canavari, R.J., Laubie, M.J., Le Douareg, J.C., 1968. Synthesis and vasodilator activity of new piperazine derivatives. J. Med. Chem. 11(6), 1151-1155.
Rockenbach, J., Nahrstedt, A., Wray, V., 1992. Cyanogenic glycosides from Psydrax and Oxyanthus species. Phytochemistry 31(2), 567-570.
Saso, L., Valentini, G., Casini, M., Grippa E., Gatto, M.T., Leone, M., Silvestrini, B., 2001. Inhibition of heat-induced denaturation of albumin by nonsteroidal antiinflammatory drugs ( NSAIDs ): Pharmacological implications. Arch. Pharm. Res. 24, 150-151.
Sotnikova R., Kettmann V., Kostalova D., Taborska E., 1997. Relaxant properties of some aporphine alkaloids from Mahonia aquifolium. Methods Find. Exp. Clin. Pharmacol. 19, 589-597.
Song, M.C., Yang, H.J., Jeong, T.S., Kim, K.T., Baek, N.I., 2008. Heterocyclic compounds from Chrysanthemum coronarium L. and their inhibitory activity on hACAT-1 hACAT- 2, and LDL-oxidation. Arch. Pharm. Res. 31, 573-578.
Tamekoa, M.J.E., Chouna, J.R., Nkeng-Efouet, A.P., Tapondjou, A.L., Sewald, N., 2017. Furan derivatives from Lannea kerstingii. Phytochem. Lett. 20, 282-284
Trinh, T.T., Tran, V.S., Katrin, F., Ludger, W., 2008. Triterpenes from the roots of codonopsis pilosula. J. Chem. 46(4), 515-520.
Viegas Jr, C., Da S. Bolzani, V., Furlan, M., Barreiro, E.J., Young, M.C.M., Tomazela, D., Eberlin, M.N., 2004. Further bioactive piperidine alkaloids from the flowers and green fruits of Cassia spectabilis. J. Nat. Prod. 67, 908-910.
Wodtke, R., Steinberg, J., Kockerling, M., Loser, R., Mamat, C., 2018. NMR-based investigations of acyl-functionalized piperazines concerning their conformational behavior in solution. Roy. Soc. Chem. Adv. 8, 40921-40933.
Yen, C.K., Keng, C.W., Hasnah, O., Ibrahim, E., Mohammad, Z.A., 2013. Chemical constituents and biological activities of Strobilanthes crispus L. Rec. Nat. Prod. 7(1), 59-64.
Yun, H.M., Shu, X.J., Chen, G.Y., Ji, M.H., Ding, J.Y., 2014. Chemical constituents from barks of Lannea coromandelica. Chin. Herb. Med. 6, 65-69.