Capsaicin Derivatives Containing Indole and Nitroindole for Improved Anti-Inflammatory Activity

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Chaiyot - Mukthung Sirirat Chancharunee Filip Kielar Sutatip Pongcharoen Uthai Wichai

Abstract

     In this investigation, capsaicin derivatives which containing indole or nitroindole in the tail region and a nitro group on the 4-hydroxybenzyl residue at the head region, were designed to mimic the benzyl residue at the terminal part of the daphnane diterpenoid moiety in resiniferatoxin (RTX). The novel capsaicin derivatives were readily synthesized using the peptide coupling reaction between heterocyclic acetic acid derivatives and benzylamine derivatives with moderate yield. Furthermore, novel capsaicin derivatives were evaluated for their ability to inhibit the production of tumor necrosis factor-alpha (TNF-alpha, one of the pro-inflammatory cytokines, by lipopolysaccharides (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) in which the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) channel is present. It was found that capsaicin derivatives containing nitroindole in the tail region and a nitro group on the 4-hydroxybenzyl residue at the head region exhibited the highest activity for inhibition of TNF-alpha production, in comparison with capsaicin, giving reductions from 47.65%-51.95% and basis for this significant enhancement of the anti-inflammatory activity could potentially originate from the promotion of binding with TRPV1 on PBMCs through p-p stacking interactions provided from the nitrobenzylic and nitroindole residues at both ends.


Keywords: Capsaicin, TNF-alpha, TRPV1, anti-inflammatory activity

References

Anand, P., & Bley, K. (2011). Topical capsaicin for pain management: therapeutic potential and mechanisms of action of the new high-concentration capsaicin 8% patch. BJA: British Journal of Anaesthesia, 107(4), 490-502. doi:10.1093/bja/aer260
Crossley, F. S., & Moore, M. L. (1944). Studies on the leuckart reaction. The Journal of Organic Chemistry, 9(6), 529-536. doi:10.1021/jo01188a006
Devesa, I., Planells-Cases, R., Fernández-Ballester, G., González-Ros, J. M., Ferrer-Montiel, A., & Fernández-Carvajal, A. (2011). Role of the transient receptor potential vanilloid 1 in inflammation and sepsis. Journal of Inflammation Research, 4, 67-81. doi:10.2147/JIR.S12978
Engler, A., Aeschlimann, A., Simmen, B. R., Michel, B. A., Gay, R. E., Gay, S., & Sprott, H. (2007). Expression of transient receptor potential vanilloid 1 (TRPV1) in synovial fibroblasts from patients with osteoarthritis and rheumatoid arthritis. Biochem Biophys Res Commun, 359(4), 884-888. doi: 10.1016/j.bbrc.2007.05.178
Fan, X., You, J., Kang, J., Ou, Q., & Zhu, Q. (1998). New reagents for determination of amino acids by liquid chromatography with pre-column fluorescence derivatization. Analytica Chimica Acta, 367(1–3), 81-91. doi:http://dx.doi.org/10.1016/S0003-2670(98)00125-1
Hougee, S., Sanders, A., Faber, J., Graus, Y. M., van den Berg, W. B., Garssen, J., . . . Hoijer, M. A. (2005). Decreased pro-inflammatory cytokine production by LPS-stimulated PBMC upon in vitro incubation with the flavonoids apigenin, luteolin or chrysin, due to selective elimination of monocytes/macrophages. Biochem Pharmacol, 69(2), 241-248. doi:10.1016/j.bcp.2004.10.002
Icke, R. N., Redemann, C. E., Wisegarver, B. B., & Alles, G. A. (2003). m-Nitrobenzaldehyde Dimethylacetal Organic Syntheses: John Wiley & Sons, Inc.
Kim, C.-S., Kawada, T., Kim, B.-S., Han, I.-S., Choe, S.-Y., Kurata, T., & Yu, R. (2003). Capsaicin exhibits anti-inflammatory property by inhibiting IkB-a degradation in LPS-stimulated peritoneal macrophages. Cellular Signalling, 15(3), 299-306. doi:http://doi.org/10.1016/S0898-6568 (02)00086-4
Kim, Y., & Lee, J. (2014). Anti-Inflammatory Activity of Capsaicin and Dihydrocapsaicin through Heme Oxygenase-1 Induction in Raw264.7 Macrophages. Journal of Food Biochemistry, 38(4), 381-387. doi:10.1111/jfbc.12064
Leung, F. W. (2014). Capsaicin as an anti-obesity drug. Prog Drug Res, 68, 171-179.
Liao, M., Cao, E., Julius, D., & Cheng, Y. (2013). Structure of the TRPV1 ion channel determined by electron cryo-microscopy. Nature, 504(7478), 107-112. doi:10.1038/nature12822
Loakes, D., & Brown, D. M. (1994). 5-Nitroindole as an universal base analogue. Nucleic Acids Research, 22(20), 4039-4043.
Loakes, D., Brown, D. M., Linde, S., & Hill, F. (1995). 3-Nitropyrrole and 5-nitroindole as universal bases in primers for DNA sequencing and PCR. Nucleic Acids Research, 23(13), 2361-2366.
Maihofner, C., & Heskamp, M. L. (2013). Prospective, non-interventional study on the tolerability and analgesic effectiveness over 12 weeks after a single application of capsaicin 8% cutaneous patch in 1044 patients with peripheral neuropathic pain: first results of the QUEPP study. Curr Med Res Opin, 29(6), 673-683. doi:10.1185/03007995.2013.792246
Montell, C. (2001). Physiology, phylogeny, and functions of the TRP superfamily of cation channels. Sci STKE, 2001(90), 1. doi:10.1126/stke.2001.90.re1
Nelson., E. K. (1919). "The constitution of capsaicin, the pungent principle of capsicum". Journal of the American Chemical Society, 41, 1115-1121.
Sharma, S. K., Vij, A. S., & Sharma, M. (2013). Mechanisms and clinical uses of capsaicin. Eur J Pharmacol, 720(1-3), 55-62. doi:10.1016/j.ejphar.2013.10.053
Shimazaki, Y., Yajima, T., Takani, M., & Yamauchi, O. (2009). Metal complexes involving indole rings: Structures and effects of metal–indole interactions. Coordination Chemistry Reviews, 253(3), 479-492. doi:https://doi.org/10.1016/j.ccr.2008.04.012
Thresh, J. C. (1876). Isolation of capsaicin. The Pharmaceutical Journal and Transactions, 6(3), 941-947.
Tsuji, F., & Aono, H. (2012). Role of Transient Receptor Potential Vanilloid 1 in Inflammation and Autoimmune Diseases. Pharmaceuticals, 5(8), 837-852. doi:10.3390/ph5080837
Vanier, G. S. ( 2007). Simple and Efficient Microwave-Assisted Hydrogenation Reactions at Moderate Temperature and Pressure. Synlett, 1, 131–135. doi:10.1055/s-2006-958428
Wheaton, C. A., Dobrowolski, S. L., Millen, A. L., & Wetmore, S. D. (2006). Nitrosubstituted aromatic molecules as universal nucleobases: Computational analysis of stacking interactions. Chemical Physics Letters, 428(1), 157-166. doi:https://doi.org/10.1016/j.cplett.2006.07.051
Wichai, U. (2003). Synthesis and Investigation of PNA-DNA Complexes Containing Novel Aromatic Residues: University of Alabama.
Winter, J., Bevan, S., & Campbell, E. A. (1995). Capsaicin and pain mechanisms. Br J Anaesth, 75(2), 157-168.
Yang, F., Xiao, X., Cheng, W., Yang, W., Yu, P., Song, Z., . . . Zheng, J. (2015). Structural mechanism underlying capsaicin binding and activation of the TRPV1 ion channel. Nat Chem Biol, 11(7), 518-524. doi:10.1038/nchembio.1835

Section
Research Articles

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How to Cite
MUKTHUNG, Chaiyot - et al. Capsaicin Derivatives Containing Indole and Nitroindole for Improved Anti-Inflammatory Activity. Naresuan University Journal: Science and Technology (NUJST), [S.l.], v. 26, n. 3, p. 157-169, sep. 2018. ISSN 2539-553X. Available at: <http://www.journal.nu.ac.th/NUJST/article/view/Vol-26-No-3-2018-157-169>. Date accessed: 13 dec. 2018. doi: https://doi.org/10.14456/nujst.2018.3.