The Clitocybins and 2-Substituted-Isoindolin-1-Ones: Synthesis and in Vitro Antimycobacterial Activities
Keywords:Isoindolinone, Tuberculosis, Clitocybins, Cytotoxicity, Antibiotics
Despite strong indications of antimycobacterial activities for clitocybins reported since 1945, no reports linking chemical structure and activity have been reported in the literature since then. In this study, we synthesized some clitocybin derivatives (also called 2-substituted-isoindolinones), and tested their activities and carried out some chemical derivations. Isoindolinones were prepared from methyl 2-formyl-3,5-dimethoxybenzoate and various primary aromatic amines. Compounds were evaluated for in vitro activity against Mycobacterium tuberculosis H37Rv, as well as for cytotoxicity (CC50) on the Vero cell line. 4,6-dihydroxy-2-(4-hydroxyphenyl)isoindolin-1-one, 7, and 4-hydroxy-2-(4-hydroxyphenyl)-6-methoxy-isoindol-1-one, 5, exhibited the highest antimycobacterial activities (minimum inhibitory concentration = 19.45 µM and 18.45 µM, respectively) and were non-toxic (CC50 = 30 µM and 29 µM, respectively).
WHO: Global tuberculosis report 2013: http://www.who.int/tb/publications/global_report/en/index.html
Ch. Hollande, Mass lysis of Koch's bacilli in the guinea-pig after treatment with clitocybin. Inhibitory property of this product in respect of the typhus bacillus, the coli bacillus, Brucella abortus, c., C. R. Acad. Sc. Paris 221 (1945) 361-363.
A.Ch. Hollande, La bacteriostase et la bacteriolyse du bacille tuberculeux par la Clitocybine, C. R. Acad. Sc. Paris 224 (1947) 1534-1535.
Ch. Hollande, A propos de la clitocybine cristallisée, C. R. Acad. Sc. Paris 228 (1949) 1758-1760.
A.F. Rebert, Recherches sur la clitocybine contenue dans les carpophores de clitocybe candida, Doctoral Thesis (Pharmacie), Montpellier, 1949.
A.F. Rebert, J.C. Ringenbach, A. Ch. Hollande. Isolement d’un hetroside du mycelium de Clitocybe gigantea. Trav. Soc. Pharm. Montpellier 16 (1956) 161-163.
J.C. Ringenbach, Contribution à l’étude du Clitocybe gigantea (Fries ex Sowerby) Gillet et de ces principes antibiotiques, Doctoral Thesis (Pharmacie). Strasbourg 1962, 1-104.
M. Anchel, A. Hervey, W.J. Robbins, Antibiotic substances from Basidiomycetes VII. Clitocybe illudens, Proc. Natl. Acad. Sci. USA. 36 (1950) 300-305.
W.R. Müller-Stoll, The antibiotic activity of clitocybine and nebularine from leucopaxillus giganteus and clitocybe nebularis, Zeitschrift Fuer Mykologie 56 (1990) 167-186.
J. Pohleven, N. Obermajer, J. Sabotic, S. Anzlovar, K. Sepcić, J. Kos, B. Kralj, B. Strukelj, J. Brzin, Purification, characterization and cloning of a ricin B-like lectin from mushroom Clitocybe nebularis with antiproliferative activity against human leukemic T cells, Biochim. Biophys. Acta. 1790 (2009) 173-181.
E.Y. Moon, J.M. Oh, Y.H. Kim, I.J. Ryoo, I.D. Yoo, Clitocybins, novel isoindolinone free radical scavengers, from mushroom Clitocybe aurantiaca inhibit apoptotic cell death and cellular senescence, Biol. Pharm. Bull. 32 (2009) 1689-1694.
Y.H. Kim,, S.M. Cho, J.W. Hyun, I.J. Ryoo, S.J. Choo, S. Lee, S.J. Seok, J.S. Hwang, E.D. Sohn, B.S. Yun, K.H. Bae, I.D. Yoo. A new antioxidant, clitocybin A, from the culture broth of Clitocybe aurantiaca, J. Antibiot. (Tokyo) 61 (2008) 573-576.
K.H. Kim, H.J. Noh, S.U. Choi, K.R. Lee, Isohericenone, a new cytotoxic isoindolinone alkaloid from Hericium erinaceum, J. Antibio. 65 (2012) 575-577.
K.D. Yoo, E.S. Park, Y. Lim, S.I. Kang, S.H. Yoo, H.H. Won, Y.H. Kim, I.D. Yoo, H.S. Yoo, J.T. Hong, Y.P. Yun, Clitocybin A, a novel isoindolinone, from the mushroom Clitocybe aurantiaca, inhibits cell proliferation through G1 phase arrest by regulating the PI3K/Akt cascade in vascular smooth muscle cells, J. Pharmacol. Sci. 118 (2012), 171-177.
K.D. Yoo, E.S. Park, Y. Lim, S.I. Kang, S.H. Yoo, H.H. Won, H.P. Lee, Y.H. Kim, I.D. Yoo, H.S. Yoo, clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-RB phosphorylation, Vascul. Pharmacol. 56 (2012) 91-97.
Y.H. Kim, I.J. Ryoo, S.J. Choo, G.H. Xu, S. Lee, S.J. Seok, K. Bae, I.D. Yoo, Clitocybin D, a novel human neutrophil elastase inhibitor from the culture broth of Clitocybe aurantiaca, J. Microbiol. Biotechnol. 19 (2009) 1139-1141.
I.D. Yoo, I.J. Ryoo, Y.H. Kim, S.J. Choo, S. Lee, Novel clitocybin derivatives, preparation method thereof and composition containing the extract of clitocybe aurantiaca Kctc 11143bp or the novel clitocybin derivatives for prevention of aging as an active ingredient. Korea Res. Inst. Patent WO 2009102083.
ALOGPS 21; http://www.virtuallaboratory.org/lab/alogps/; access date 10-11 July 2009.
J. Bouquet, M. Rivaud, S. Chevalley, E. Deharo, V. Jullian, A. Valentin, Biological activities of nitidine, a potential anti-malarial lead compound, Malaria J. 11 (2012) 67.
How to Cite
All articles published in Journal of Advances in Linguistics are licensed under a Creative Commons Attribution 4.0 International License.