Login Register Cart 0
Generic placeholder image

Letters in Drug Design & Discovery

Editor-in-Chief

ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Analgesic Activity of Monoterpenoid Aldehyde-derived Hydro-2H-chromeneols

Author(s): Irina Il'ina*, Ekaterina Morozova, Dina Korсhagina, Konstantin Volсho, Tat'yana Tolstikova and Nariman Salakhutdinov

Volume 17, Issue 1, 2020

Page: [68 - 78] Pages: 11

DOI: 10.2174/1570180816666181114131220

Abstract

Background: Despite a variety of drugs used to stop acute pain, problems related to their insufficient efficacy and undesirable side effects have remained unresolved. Therefore, the search for analgesics of new structural types, which combine high activity with low toxicity, is a topical issue. It is known that a number of compounds with a hydrogenated 2H-chromene skeleton exhibit significant analgesic activity in in vivo tests.

Methods: New hydro-2H-chromenols containing monoterpenoid moieties were obtained via one-pot synthesis by the interaction between para-menthane alcohols and commercially available monoterpene aldehydes: Citral, hydroxycitronellal, myrtenal, and perillaldehyde. The analgesic activity of these compounds wаs studied in the acetic acid-induced writhing test and hot plate test.

Results: The target compounds were characterized using NMR and HR-MS. Most of them exhibited pronounced analgesic activity.

Conclusion: Due to high analgesic activity, (2S,4aR,8R,8aR)-2-((E)-2,6-dimethylhepta-1,5-dien-1- yl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diol is considered as candidate compound to participate in further research.

Keywords: Monoterpenoid aldehyde, isopulegol, chromene, analgesia, acetic acid-induced writhing test, hot-plate test.

« Previous Next »
Graphical Abstract

[1]
Stewart, W.F.; Ricci, J.A.; Chee, E.; Morganstein, D.; Lipton, R. Lost productive time and cost due to common pain conditions in the US workforce. JAMA, 2003, 290(18), 2443-2454.
[http://dx.doi.org/10.1001/jama.290.18.2443] [PMID: 14612481]
[2]
Moore, N.D. In search of an ideal analgesic for common acute pain. Acute Pain, 2009, 11, 129-137.
[http://dx.doi.org/10.1016/j.acpain.2009.09.003]
[3]
Szychowski, J.; Truchon, J-F.; Bennani, Y.L. Natural products in medicine: Transformational outcome of synthetic chemistry. J. Med. Chem., 2014, 57(22), 9292-9308.
[http://dx.doi.org/10.1021/jm500941m] [PMID: 25144261]
[4]
Mikhalchenko, O.S.; Volcho, K.P.; Salakhutdinov, N.F. Synthesis of heterocyclic compounds by interaction of aldehydes with monoterpenoids.In:New Developments in Aldehydes Research; Torrioni, L.; Pescasseroli, E., Eds.; Nova Science Publishers: New York, 2013, pp. 49-80.
[5]
Salakhutdinov, N.F.; Volcho, K.P.; Yarovaya, O.I. Monoterpenes as a renewable source of biologically active compounds. Pure Appl. Chem., 2017, 89, 1105-1118.
[http://dx.doi.org/10.1515/pac-2017-0109]
[6]
Salakhutdinov, N.F.; Volcho, K.P.; Il’ina, I.V.; Korchagina, D.V.; Tatarova, L.E.; Barkhash, V.A. New reactions of isoprenoid olefins with aldehydes promoted by Al2O3-SiO2 catalysts. Tetrahedron, 1998, 54, 15619-15642.
[http://dx.doi.org/10.1016/S0040-4020(98)00977-6]
[7]
Patrusheva, O.S.; Volcho, K.P.; Salakhutdinov, N.F. Approaches to the synthesis of oxygen-containing heterocyclic compounds based on monoterpenoids. Russ. Chem. Rev., 2018, 87(8), 771-796.
[http://dx.doi.org/10.1070/RCR4810]
[8]
Hamann, L.G.; Meyer, J.H.; Ruppar, D.A.; Marschke, K.B.; Lopez, F.J.; Allegretto, E.A.; Karanewsky, D.S. Structure-activity relationships and sub-type selectivity in an oxabicyclic estrogen receptor α/β agonist scaffold. Bioorg. Med. Chem. Lett., 2005, 15(5), 1463-1466.
[http://dx.doi.org/10.1016/j.bmcl.2004.12.077] [PMID: 15713407]
[9]
Mikhalchenko, O.; Il’ina, I.; Pavlova, A.; Morozova, E.; Korchagina, D.; Tolstikova, T.; Pokushalov, E.; Volcho, K.; Salakhutdinov, N. Synthesis and analgesic activity of new heterocyclic compounds derived from monoterpenoids. Med. Chem. Res., 2013, 22, 3026-3034.
[http://dx.doi.org/10.1007/s00044-012-0310-9]
[10]
Il’ina, I.; Mikhalchenko, O.; Pavlova, A.; Korchagina, D.; Tolstikova, T.; Pokushalov, E.; Volcho, K.; Salakhutdinov, N. Highly potent analgesic activity of monoterpene-derived (2S,4aR,8R,8aR)-2-aryl-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols. Med. Chem. Res., 2014, 23, 5063-5073.
[http://dx.doi.org/10.1007/s00044-014-1071-4]
[11]
Pavlova, A.; Mikhalchenko, O.; Rogachev, A.; Il’ina, I.; Korchagina, D.; Gatilov, Yu.; Tolstikova, T.; Volcho, K.; Salakhutdinov, N. Synthesis and analgesic activity of stereoisomers of 2-(3(4)-hydroxy-4(3)-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromene-4,8-diols. Med. Chem. Res., 2015, 24, 3821-3830.
[http://dx.doi.org/10.1007/s00044-015-1426-5]
[12]
Il’ina, I.; Pavlova, A.; Korchagina, D.; Ardashov, O.; Tolstikova, T.; Volcho, K.; Salakhutdinov, N. Synthesis and analgesic activity of monoterpenoid-derived alkyl-substituted chiral hexahydro-2H-chromenes. Med. Chem. Res., 2017, 26, 1415-1426.
[http://dx.doi.org/10.1007/s00044-017-1847-4]
[13]
Pavlova, A.V.; Nazimova, E.V.; Mikhal’chenko, O.S.; Il’ina, I.V.; Korchagina, D.V.; Ardashov, O.V.; Morozova, E.A.; Tolstikova, T.G.; Volcho, K.P.; Salakhutdinov, N.F. Synthesis and analgesic activity of 4,7-dimethyl-3,4,4a,5,8,8a-hexahydro-2H-chromen-4,8-diols containing thiophene substituents. Chem. Nat. Compd., 2016, 52, 813-820.
[http://dx.doi.org/10.1007/s10600-016-1785-2]
[14]
Nazimova, E.; Pavlova, A.; Mikhalchenko, O.; Il’ina, I.; Korchagina, D.; Tolstikova, T.; Volcho, K.; Salakhutdinov, N. Discovery of highly potent analgesic activity of isopulegol-derived (2R,4aR,7R,8aR)-4,7-dimethyl-2-(thiophen-2-yl)octahydro-2H-chromen-4-Ol. Med. Chem. Res., 2016, 25(7), 1369-1383.
[http://dx.doi.org/10.1007/s00044-016-1573-3]
[15]
Pavlova, A.; Patrusheva, O.; Il’ina, I.; Volcho, K.; Tolstikova, T.; Salakhutdinov, N. The decisive role of mutual arrangement of hydroxy and methoxy groups in (3(4)-hydroxy-4(3)-methoxyphenyl)-4,7-dimethyl-3,4,4a,5,8,8ahexahydro-2H-chromene-4,8-diols in their biological activity. LDDD, 2017, 14, 508-514.
[http://dx.doi.org/10.2174/1570180813666161102142642]
[16]
Slater, S.; Lasonkar, P.B.; Haider, S.; Alqahtani, M.J.; Chittiboyina, A.G.; Khan, I.A. One-step, stereoselective synthesis of octahydrochromanes via the Prins reaction and their cannabinoid activities. Tetrahedron Lett., 2018, 59(9), 807-810.
[http://dx.doi.org/10.1016/j.tetlet.2018.01.040] [PMID: 29880989]
[17]
Il’ina, I.V.; Volcho, K.P.; Korchagina, D.V.; Barkhash, V.A.; Salakhutdinov, N.F. Reactions of allyl alcohols of the pinane series and of their epoxides in the presence of montmorillonite clay. Helv. Chim. Acta, 2007, 90, 353-368.
[http://dx.doi.org/10.1002/hlca.200790042]
[18]
Il’ina, I.V.; Volcho, K.P.; Korchagina, D.V.; Salakhutdinov, N.F. The convenient way for obtaining geranial by acid-catalyzed kinetic resolution of citral. Helv. Chim. Acta, 2016, 99, 373-377.
[http://dx.doi.org/10.1002/hlca.201500266]
[19]
Wehrly, F.W.; Nishida, T. The Use of carbon-13 nuclear magnetic resonance spectroscopy in natural products chemistry. Int. J. Pharm., 1979, 35, 207-210.
[http://dx.doi.org/10.1007/978-3-7091-3265-4_1]
[20]
Rochat, S.; Minardi, C.; de Saint Laumer, J-Y.; Herrmann, A. Controlled release of perfumery aldehydes and ketones by norrish type-ii photofragmentation of α-keto esters in undegassed solution. Helv. Chim. Acta, 2000, 83, 1645-1671.
[http://dx.doi.org/10.1002/1522-2675(20000705)83:7<1645:AID-HLCA1645>3.0.CO;2-S]
[21]
Barr, K.J.; Berk, S.C.; Buchwald, S.L. Titanocene-catalyzed reduction of esters using polymethylhydrosiloxane as the stoichiometric reductant. J. Org. Chem., 1994, 59, 4323-4326.
[http://dx.doi.org/10.1021/jo00094a056]
[22]
Knapp, H.; Straubinger, M.; Fornari, S.; Oka, N.; Watanabe, N.; Winterhalter, P. (S)-3,7-Dimethyl-5-octene-1,7-diol and related oxygenated monoterpenoids from petals of Rosa damascena mill. J. Agric. Food Chem., 1998, 46, 932-940.
[http://dx.doi.org/10.1021/jf970987x]
[23]
Kutner, A.; Zhao, H.; Fitak, H.; Wilson, S.R. Synthesis of retiferol RAD1 and RAD2, the lead representatives of a new class of des-CD analogs of cholecalciferol. Bioorg. Chem., 1995, 23, 22-32.
[http://dx.doi.org/10.1006/bioo.1995.1002]
[24]
Eddy, N.B.; Leimbach, D. Synthetic analgesics. II. dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. Exp. Ther., 1953, 107(3), 385-393.
[PMID: 13035677]
[25]
Khvostov, M.V.; Borisov, S.A.; Tolstikova, T.G.; Dushkin, A.V.; Tsyrenova, B.D.; Chistyachenko, Y.S.; Polyakov, N.E.; Dultseva, G.G.; Onischuk, A.A.; An’kov, S.V. Supramolecular complex of ibuprofen with larch polysaccharide arabinogalactan: Studies on bioavailability and pharmacokinetics. Eur. J. Drug Metab. Pharmacokinet., 2017, 42(3), 431-440.
[http://dx.doi.org/10.1007/s13318-016-0357-y] [PMID: 27351190]
[26]
Tolstikova, T.G.; Pavlova, A.V.; Morozova, E.A.; Khomenko, T.M.; Volcho, K.P.; Salakhutdinov, N.F. The analgesic activity of 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepine-6-amine and its hydrochloride. Lett. Drug Des. Discov., 2012, 9, 513-516.
[http://dx.doi.org/10.2174/157018012800389296]
[27]
Surburg, H.; Panten, J. Common Fragrance and Flavors Materials, 5th ed; Wiley-VCH: Weinheim, Germany, 2006.
[http://dx.doi.org/10.1002/3527608214]
[28]
Noyori, R. Green Chem., 2003, 5, G37-G39.
[http://dx.doi.org/10.1039/b305339n]
[29]
da Silva, K.A.; Robles-Dutenhefner, P.A.; Sousa, E.M.B.; Kozhevnikova, E.F.; Kozhevnikov, I.V.; Gusevskaya, E.V. Cyclization of (+)-citronellal to (−)-isopulegol catalyzed by H3PW12O40/SiO2. Catal. Commun., 2004, 5, 425-429.
[http://dx.doi.org/10.1016/j.catcom.2004.05.001]
[30]
Lenardão, E.J.; Botteselle, G.; de Azambuja, V.; Perin, G.; Jacob, R.G. Citronellal as key compound in organic synthesis. Tetrahedron, 2007, 63, 6671-6712.
[http://dx.doi.org/10.1016/j.tet.2007.03.159]

Rights & Permissions Print Cite
Article Metrics
22
2
© 2024 Bentham Science Publishers | Privacy Policy