Natural and Synthesized Indole Derivatives and their Biological Activities
Abstract
Indole compounds are found widely in nature, particularly in plants, bacteria, fungi, and animals, and many of them have significant pharmacological or physiological effects. These indole compounds also have been synthesized by the various methods and reported as a most bioactivities compounds. This manuscript provides a comprehensive overview of the natural sources, synthesis way, biological activities, and therapeutic potential of bioactive indoles, with a focus on their relevance in drug discovery and human health. In this paper, we have reviewed biological activities indole compounds with two categories bases on bioactivities of natural and synthesized indole derivatives.
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References
A. Baeyer, "Ueber die Reduction aromatischer Verbindungen mittelst Zinkstaub". Ann. 140, 295, doi: 10.1002/jlac.18661400306 (1866).
A. Baeyer, A. Emmerling, "Synthese des Indols". Chemische Berichte 2, 679, doi: 10.1002/cber.186900201268 (1869).
Quin L. D.; Tyrell J. In Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals; John Wiley & Sons, Inc., 2010; p. 170.
Lakhdar, S.; Westermaier, M.; Terrier, F.; Goumont, R.; Boubaker, T.; Ofial, A. R.; Mayr, H. J. Org. Chem. 2006, 71, 9088–9095.
Alvarez-Builla, J.; Vaquero, J.; Barluenga, J. Modern Heterocyclic Chemistry; Wiley-VCH Verlag & Co. KGaA, 2011.
Sundberg, R. J. Indoles; Acedemic Press: New York, 1996.
Robert, M., F., Wink, M. Alkaloids: Biochemistry, Ecology, and Medicinal Applications: Plenum: London, 1998.
Von Nussbaum, F. Angew. Chem., Int. Ed. 2003, 42, 3068-3071.
Pindur, U.; Lemster, T. Curr. Med. Chem. 2001, 8, 1681-1698.
http://www.leffingwell.com/olfact5.htm
Hesse, M. Alkaloids. Nature’s Curse of Blessing; Wiley-VCH: Weinheim, 2002.
Hibino, S.; Choshi, T. Nat. Prod. Rep. 2002, 19, 148–180.
Gilchrist T. L., Heterocyclic Chemistry, second Edition, Longman Scientific & Technical, UK, 1993
Joule J.A., Mills K., Heterocyclic Chemistry, fourth Edition, Blackwell Publishing, 2000
Römpp Chemie Lexikon, Neunte Auflage, Thieme Verlag, 1991.
Della, G.; Djura, P.; Sargent, M.V.J. Chem. Soc., Perkin Trans. I 1981, 1679.
Fusetani, N.; Sugawara, T.; Matsunaga, S.J. Org. Chem. 1991, 56, 4971-4974.
Guerriero, A.; D’Ambrosio, M.; Pietra, F.; Debitus, C.; Ribes, O.J. Nat. Prod 1993, 56, 1962-1970.
Bobzin, S. C. Faulkner, D. J. J. Org. Chem. 1991, 56, 4403-4407.
Rashotte, Aaron M; Poupart, Julie; Waddell, Candace S; Muday, G. K. Plant Physiol. 2003, 133, 761–772.
Schlittler, E. In The Alkaloids: Chemistry and Physiology; Academic Press, 1965; Vol. 8, pp. 287–334.
Ferlin, M. G.; Marzano, C.; Gandin, V.; Dall’Acqua, S.; Ferlin, M. G.; Marzano, C.; Gandin, V.; Dall'Acqua, S.; Dalla Via, L. Chem. Med. Chem. 2009, 4, 363–377.
Gul, W.; Hamann, M. T. Life Sci. 2005, 78, 442–453.
G. R. Humphrey, J. T. Kuethe, Chem. Rev., 106, 2875-2911 (2006).
A. L. Smith, G. I. Stevenson, C. J. Swain, J. L. Castro, Tet. Lett., 39, 8317-8320 (1998).
D. A. Horton, G. T. Bourne, M. L. Smythe, Chem. Rev., 103, 893-930 (2003).
A. A. R. Mohamed, A. R. Eman, M. S. Nermien, M. El-Shenawy Siham, Bioorg. Med. Chem., 15(11), 3832-3841 (2007).
M. Susumu, T. Tatsuo, H. Tsunetoshi, H. Yoshiharu, O. Toshihiko, H. Hiroshi, K. Shiro,
Masanao, A. Akinori, Y. Kiyoshi, J. Med. Chem., 46(12), 2446-2455 (2003).
A. Gopalakrishnan, A. Shanmugasundaram, J. Yeon Tae, Bioorg. Med. Chem. Lett., 20(7), 2242-2249 (2010).
S. Jakob Avi, B. Meir, Y. Boris, Bioorg. Med. Chem., 16(11), 6297-6305 (2008).
X. Hui, F. Ling-ling, Eur. J. Med. Chem., 46(1), 364-369 (2011).
Jr. S. Alejandro, J. M. Kelly, D. A. Brett, L. Brian, D. B. Jamin, L. M. Kirsten, M. E. Anita, N. Diane, A. L. Michael, L. Alice, Bioorg. Med. Chem. Lett., 20(21), 6226-6230 (2010).
H. Youssef, C. Giovanni, B. Joan, R. Gloria, P. Salvatore, R. Demetrio, C. Maria Grazia, P. Ramon, P. Maria Dolors, J. Med. Chem., 53(18), 6560-6571 (2010).
A. Aldo, B. Silvia, G. Massimiliano, L. Alberto, L. Alessandra, M. Rita, R. Mirella, V. Lucilla, L. Laura, P. Cecilia, Bioorg. Med. Chem., 18(9), 3004-3011 (2010).
G. Michele, B. Alessandro, M. Mauro, L. C. Paolo, I. Cristina, L. Roberta, Antiviral Research, 83(2), 179-185 (2009).
M. Tatsuya, O. Kenichi, H. Masahiko, M. Tetsuo, T. Toshiyuki, O. Mitsuaki, Eur. J. Med. Chem., 44(6), 2533-2543 (2009).
S. K. Agarwal, A. K. Saxena, P. C. Jain, N. Anand, R. C. Srimal, B. N. Dhawan, Indian J. Chem.: B, 30B(4), 413-416 (1991).
K. Sharma, R. Jain, K. C. Joshi, Indian J. Het. Chem., 1(4), 189-192 (1992).
J. Debray, W. Zeghida, B. Baldeyrou, C. Mahieu, A. Lansiaux, M. Demeunynck, Bioorg. Med. Chem. Lett., 20(14), 4244-4247 (2010).
B. T. Ratan, A. Balasubramani, Y. Perumal, S. Dharmarajan, Bioorg. Med. Chem. Lett., 15(20), 4451-4455 (2005). 45. W. E. Kreighbaum, W. L. Matier, R. D. Dennis, J. L. Minielli, D. David; Jr. J. L. Perhach, C. T. William, J. Med. Chem., 23(3), 285-289 (1980).
A. Ioanna, T. K. Anna, S. Eleni, S. Theodora, Chemical & Pharmaceutical Bulletin, 51(10), 1128-1131 (2003).
O. Sureyya, K. Zuhal, A. O. Ahmet, C, Tulay, Arch. Pharm., 340(3), 140-146 (2007).
G. R. Humphrey, J. T. Kuethe, Chem. Rev., 106, 2875-2911 (2006).
Dahlöf, C. Therapy 2005, 2, 349–356.
Ferreira, S.; Moncada, S.; Vane, J. Indomethacin and aspirin abolish prostaglandin release fromthe spleen. Nat. New Biol. 1971, 231, 237–239.
Johnson, I.S.; Armstrong, J.G.; Gorman, M.; Burnett, J.P. Jr. The Vinca Alkaloids: A new class of oncolytic agents. Cancer Res. 1963, 23, 1390–1427.
Gilmore DL, Liu Y, Matsumoto RR. Review of the pharmacological and clinical profile of rimcazole. CNS Drug Rev. 2004 Spring;10(1):1-22.
Eaton MJ, Lookingland KJ, Moore KE (1996). "The sigma ligand rimcazole activates noradrenergic neurons projecting to the paraventricular nucleus and increases corticosterone secretion in rats". Brain Res. 733 (2): 162–6. doi:10.1016/0006-8993(96)00290-9. PMID 8891298.
Husbands, S. M.; Izenwasser, S; Loeloff, R. J.; Katz, J. L.; Bowen, W. D.; Vilner, B. J.; Newman, A. H. (1997). "Isothiocyanate derivatives of 9-3-(cis-3,5-dimethyl-1-piperazinyl)propylcarbazole (rimcazole): Irreversible ligands for the dopamine transporter". Journal of Medicinal Chemistry. 40 (26): 4340–46. doi:10.1021/jm9705519. PMID 9435903.
Katz JL, Libby TA, Kopajtic T, Husbands SM, Newman AH. Behavioral effects of rimcazole analogues alone and in combination with cocaine. European Journal of Pharmacology. 2003 9;468 (2):109-19.
Drugs.com International brand names for Carprofen Page accessed October 4, 2017
Carprofen/Rimadyl (Carprofen), non-steroidal, anti-inflammatory drug, Zoetis Inc.
Baruth H., et al., In anti-inflammatory and anti-rheumatic drugs, Vol. II.
Rainiford K.D., et al., newer anti-inflammatory drug, CRC press, Boca Raton, 33, 1986.
Behari, J.; Zeng, G.; Otruba W.; Thompson, M.; Muller, P.; Micsenyi, A.; Sekhon, S.; Leoni, L.; Monga, S. J. Hepatol. 2007, 46, 849–857.
William, H.; Frishman, M. D. N. Engl. J. Med. 1983, 308, 940–944. 10. Generali, J.A.; Cada, D.J. Off-label drug uses—Ondansetron: Postanesthetic shivering. Hospital Pharmacy 2009, 44, 670–671. 11. Horton, R. Lotronex and the FDA: A fatal erosion of integrity. Lancet 2001, 375, 1544–1545.
Higdon, J. V.; Delage, B.; Williams, D. E.; Dashwood, R. H. Pharmacol. Res. 2007, 55, 224–236.
Yan, X.-J.; Qi, M.; Telusma, G.; Yancopoulos, S.; Madaio, M.; Satoh, M.; Reeves, W. H.; Teichberg, S.; Kohn, N.; Auborn, K.; Chiorazzi, N. Clin. Immunol. 2009, 131, 481–494.
Park, N.l.; Kim, J. K.; Park, W. T.; Cho, J. W.; Lim, Y. P.; Park, S. U. Mol. Biol. Rep. 2011, 38, 4947–4953.
Chang, X.; Tou, J. C.; Hong, C.; Kim, H.-A.; Riby, J. E.; Firestone, G. L.; Bjeldanes, L. F. Carcinogenesis 2005, 26, 771–778.
Cope, R. B.; Loehr, C.; Dashwood, R.; Kerkvliet, N. I. Photochem. Photobiol. Sci. 2006, 5, 499–507. DOI:10.1039/B515556H.
Basanagoudar L.D., Mahajanshetti C.S., Damdal, S.B., Indian J. Chemi., Section-B, 1991, 30B, 1018-1022.
Gadient F., Diazepinoindoles ans their pharmaceutical use, Sandoz Patent G.m.b.H, Eed. Rep. Ger, De, 1985, 27.
Gatta F., Ponti F., Boll. Chem. Farm., 1981, 120, 102-107. ISSN: 0006-6648.
Chacum-Lefevre L., Joseph B., Merour J.Y., Synthesis and reactivity of azepino[3,4-b]indol-5-yl trifluoromethanesulfonate, Tetrahedron, 2000, 56(26), 4491-4499. DOI: 10.1016/S0040-4020(00)00374-4.
Joseph B., Alagille D., Merour J.Y., Leonce S., Synthesis and in Vitro Cytotoxic Evaluation of N-Substituted Benzo[5, 6]cyclohepta[b]indoles, Chem. Pharm. Bull., 2000, 48(12), 1872-1876. DOI: 10.1248/cpb.48.1872.
Joseph B., Comec O., Merour J.Y, Solans X., Font-Bardia M.J., Synthesis of 6,7‐dihydrobenzo[4,5]cyclohept‐[1,2‐b]indol‐12(5H)‐one and related compounds, Heterocycl. Chemistry, 1997, 34(2), 525-531. DOI: 10.1002/jhet.5570340229.
Hiremath S.P., Badami P.S., Purohit M.G., Indian J. Chem., Sec. B, 1984, 23B, 1058-1063.
Leboho T.C., Michael J.P., van Otterlo W.A., van Vuuren S.F., de Koning C.B., The synthesis of 2- and 3-aryl indoles and 1,3,4,5-tetrahydropyrano[4,3-b]indoles and their antibacterial and antifungal activity, Bioorganic and Medicinal Chemistry Letters, 2009, 19(17), 4948–4951. DOI: 10.1016/j.bmcl.2009.07.091.
Urgaonkar S., Cortese J.F., Barker R.H., Cromwell M., Serrano A.E., Wirth D.F., et al., A Concise Silylamine Approach to 2-Amino-3-hydroxy-indoles with Potent in vivo Antimalaria Activity, Org. Lett., 2010, 12(18), 3998–4001. DOI: 10.1021/ol101566h.
Cihan-Üstündağ G., Capan G., Synthesis and evaluation of functionalized indoles as antimycobacterial and anticancer agents, Mol. Divers., 2012, 16(3), 525–539. DOI: 10.1007/s11030-012-9385-y.
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