Development of a spectrophotometric method for assessment of the relative reactivity of monocarbonyl analogs of curcumin with 2-(dimethylamino)ethanethiol
DOI:
https://doi.org/10.20450/mjcce.2023.2638Keywords:
synthesis, monocarbonyl analogs of curcumin, thiols, Michael addition, 2-(dimethylamino)ethanethiolAbstract
In order to improve the bioavailability of curcumin, studies have been undertaken to prepare the so-called monocarbonyl analogs of curcumin (MACs) and assess their biological activity. These analogs contain an electrophilic α,β-unsaturated carbonyl moiety (Michael acceptor). Several key biological processes are connected/controlled with thiol alkylation (glutathione, cysteine, cysteine peptide residues). The most likely reaction is the Michael addition between the α,β-unsaturated acceptor and a corresponding thiol. 2,6-Bisarylidenecyclohexanone and 3,5-bisarylidenepiperidin-4-one scaffolds offer convenient tunability of electrophilicity and redox properties of the Michael acceptor by the introduction of various substituents. In this study, several MACs were prepared by Claisen-Schmidt condensation reaction, and their reactivity with 2-(dimethylamino)ethanethiol was evaluated. For this purpose, based on the UV-Vis spectra of the analogs and thiol(s), a proper method for spectrophotometric evaluation of their reactivity with 2-(dimethylamino)ethanethiol was optimized. The relative reactivity of the analogs was 7 > 2 > 5 > 4 > 1 ≈ 6. The developed method is simple, and it can be extended to assess the reactivity of other MACs.
References
(1) Goel, A.; Kunnumakkara, A. B.; Aggarwal, B. B., Curcumin as “Curecumin”: from kitchen to clinic. Biochem. Pharmacol. 2008, 75 (4), 787–809.
https://doi.org/10.1016/j.bcp.2007.08.016
(2) Wilken, R.; Veena, M. S.; Wang, M. B.; Srivatsan, E. S., Curcumin: A review of anti-cancer properties and therapeutic activity in head and neck squamous cell carcinoma. Mol. Cancer 2011, 10, 12.
https://doi.org/10.1186/1476-4598-10-12
(3) Chen, B.; Zhang, Y.; Wang, Y.; Rao, J.; Jiang, X.; Xu, Z., Curcumin inhibits proliferation of breast cancer cells through Nrf2-mediated down-regulation of Fen 1 expression. J. Steroid Biochem. Mol. Biol. 2014, 143, 11–18. https://doi.org/10.1016/j.jsbmb.2014.01.009
(4) Wang, K.; Fan, H.; Chen, Q.; Ma, G.; Zhu, M.; Zhang, X.; Zhang, Y.; Yu, J., Curcumin inhibits aerobic glycolysis and induces mitochondrial-mediated apoptosis through hexokinase II in human colorectal cancer cells in vitro. Anticancer Drugs 2015, 26 (1), 15–24
https://doi.org/10.1097/CAD.0000000000000132
(5) Shetty, D.; Kim, Y. J.; Shim, H.; Snyder, J. P., Eliminating the heart from the curcumin molecule: Monocarbonyl Curcumin Mimics (MACs). Molecules 2014, 20 (1), 249–292.
https://doi.org/10.3390/molecules20010249
(6) Das, U.; Sharma, R. K.; Dimmock, J. R., 1,5-Diaryl-3-oxo-1,4-pentadienes: a case for antineoplastics with multiple targets. Curr. Med. Chem. 2009, 16 (16), 2001–2020. https://doi.org/10.2174/092986709788682218
(7) Nelson, K. M.; Dahlin, J. L.; Bisson, J.; Graham, J.; Pauli, G. F.; Walters, M. A., The essential medicinal chemistry of curcumin. J. Med. Chem. 2017, 60 (5), 1620–1637. https://doi.org/10.1021/acs.jmedchem.6b00975
(8) Gordon, O. N.; Luis, P. B.; Sintim, H. O.; Schneider, C., Unraveling curcumin degradation: autoxidation proceeds through spiroepoxide and vinylether intermediates en route to the main bicyclopentadione. J. Biol. Chem. 2015, 290 (8), 4817–4828.
https://doi.org/10.1074/jbc.M114.618785
(9) Gordon, O. N.; Luis, P. B.; Ashley, R. E.; Osheroff, N.; Schneider, C., Oxidative transformation of demethoxy-and bisdemethoxycurcumin: products, mechanism of formation, and poisoning of human topoisomerase IIα. Chem. Res. Toxicol. 2015, 28 (5), 989–996.
https://doi.org/10.1021/acs.chemrestox.5b00009
(10) Schneider, C.; Gordon, O. N.; Edwards, R. L.; Luis, P. B., Degradation of curcumin: from mechanism to biological implications. J. Agric. Food Chem. 2015, 63 (35), 7606–7614.
https://doi.org/10.1021/acs.jafc.5b00244
(11) Hsu, C. H.; Cheng, A. L. Clinical studies with curcumin. Adv. Exp. Med. Biol. 2007, 595, 471–480. https://doi.org/10.1007/978-0-387-46401-5
(12) Zhao, C.; Liu, Z.; Liang, G., Promising curcumin-based drug design: mono-carbonyl analogues of curcumin (MACs). Curr. Pharm. Des. 2013, 19 (11), 2114–2135. https://doi.org/10.2174/138161213805289282
(13) Al-Rifai, N.; Rücker, H.; Amslinger, S., Opening or closing the lock? When reactivity is the key to biological activity. Chem. Eur. J. 2013, 19 (45), 15384–15395. https://doi.org/10.1002/chem.201302117
(14) Caprioglio, D.; Minassi, A.; Avonto, C.; Taglialatela-Scafati, O.; Appendino, G., Thiol-trapping natural products under the lens of the cysteamine assay: friends, foes, or simply alternatively reversible ligands? Phytochem. Rev. 2020, 19 (6), 1307–1321.
https://doi.org/10.1007/s11101-020-09700-w
(15) Grynkiewicz, G.; Slifirski, P., Curcumin and curcu-minoids in quest for medicinal status. Acta Biochim. Pol. 2012, 59 (2), 201–212.
(16) Gupta, S. C.; Prasad, S.; Kim, J. H.; Patchva, S.; Webb, L. J.; Priyadarsini, I. K.; Aggarwal, B. B., Multitargeting by curcumin as revealed by molecular interaction studies. Nat. Prod. Rep. 2011, 28 (12), 1937–1955. https://doi.org/10.1039/C1NP00051A
(17) Priyadarsini, K. I., Chemical and structural features influencing the biological activity of curcumin. Curr. Pharm. Des. 2013, 19 (11), 2093–2100.
(18) Iersel, M. L.; Ploemen, J. P.; Struik, I.; Van Amersfoort, C.; Keyzer, A. E.; Schefferlie, J. G.; Van Bladeren, P. J., Inhibition of glutathione s-transferase activity in human melanoma cells by alpha,beta-unsaturated carbonyl derivatives. effects of acrolein, cinnamaldehyde, citral, crotonaldehyde, curcumin, ethacrynic acid, and trans-2-hexenal. Chem. Biol. Interact. 1996, 102 (2), 117–132
(19) Sun, A.; Lu, Y. J.; Hu, H.; Shoji, M.; Liotta, D. C.; Snyder, J. P., Curcumin analog cytotoxicity against breast cancer cells: exploitation of a redox-dependent mechanism. Bioorg. Med. Chem. Lett. 2009, 19 (23), 6627–6631. https://doi.org/10.1016/j.bmcl.2009.10.023
(20) Adams, B. K.; Cai, J.; Armstrong, J.; Herold, M.; Lu, Y. J.; Sun, A.; Snyder, J. P.; Liotta, D. C.; Jones, D. P.; Shoji, M., EF 24, a novel synthetic curcumin analog, induces apoptosis in cancer cells via a redox-dependent mechanism. Anticancer Drugs 2005, 16 (3), 263–275.
https://doi.org/10.1097/00001813-200503000-00005
(21) Mosley, C. A.; Liotta, D. C.; Snyder, J. P., In: The Molecular Targets and Therapeutic Uses of Curcumin in Health and Disease; Springer US: Boston, MA, 2007; pp 77–103. https://doi.org/10.1007/978-0-387-46401-5_2
(22) Tan, X.; Sidell, N.; Mancini, A.; Huang, R.-P.; Wang, S.; Horowitz, I. R.; Liotta, D. C.; Taylor, R. N.; Wieser, F., Multiple anticancer activities of EF 24, a novel curcumin analog, on human ovarian carcinoma cells. Reprod. Sci. 2010, 17 (10), 931–940.
https://doi.org/10.1177/1933719110374239
(23) Moore, T. W.; Zhu, S.; Randolph, R.; Shoji, M.; Snyder, J. P., Liver S9 fraction-derived metabolites of curcumin analogue UBS109. ACS Med. Chem. Lett. 2014, 5 (4), 288–292. https://doi.org/10.1021/ml4002453
(24) Yin, D.-L.; Liang, Y.-J.; Zheng, T.-S.; Song, R.-P.; Wang, J.-B.; Sun, B.-S.; Pan, S.-H.; Qu, L.-D.; Liu, J.-R.; Jiang, H.-C.; Liu, L.-X., EF 24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma. Sci. Rep. 2016, 6, 32167. https://doi.org/10.1038/srep32167
(25) Chen, W.; Zou, P.; Zhao, Z.; Chen, X.; Fan, X.; Vinothkumar, R.; Cui, R.; Wu, F.; Zhang, Q.; Liang, G.; Ji, J., Synergistic antitumor activity of rapamycin and EF 24 via increasing ROS for the treatment of gastric cancer. Redox Biol 2016, 10, 78–89.
https://doi.org/10.1016/j.redox.2016.09.006
(26) Skoupa, N.; Dolezel, P.; Ruzickova, E.; Mlejnek, P., Apoptosis induced by the curcumin analogue EF-24 is neither mediated by oxidative stress-related mechanisms nor affected by expression of main drug transporters ABCB1 and ABCG2 in human leukemia cells. Int. J. Mol. Sci. 2017, 18 (11).
https://doi.org/10.3390/ijms18112289
(27) Lin, C.; Tu, C.; Ma, Y.; Ye, P.; Shao, X.; Yang, Z.; Fang, Y., Curcumin analog EF 24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma. Mol. Med. Rep. 2017, 16 (4), 4927–4933.
https://doi.org/10.3892/mmr.2017.7189
(28) He, Y.; Li, W.; Hu, G.; Sun, H.; Kong, Q., Bioactivities of EF 24, a novel curcumin analog: A review. Front. Oncol. 2018, 8, 614.
https://doi.org/10.3389/fonc.2018.00614
(29) Bertazza, L.; Barollo, S.; Mari, M. E.; Faccio, I.; Zorzan, M.; Redaelli, M.; Rubin, B.; Armanini, D.; Mian, C.; Pezzani, R., Biological effects of EF 24, a curcumin derivative, alone or combined with mitotane in adrenocortical tumor cell lines. Molecules 2019, 24 (12), 2202. https://doi.org/10.3390/molecules24122202
(30) Zhou, T.; Ye, L.; Bai, Y.; Sun, A.; Cox, B.; Liu, D.; Li, Y.; Liotta, D.; Snyder, J. P.; Fu, H.; Huang, B., Autophagy and apoptosis in hepatocellular carcinoma induced by EF25-(GSH)2: a novel curcumin analog. PLoS One 2014, 9 (9), e107876.
https://doi.org/10.1371/journal.pone.0107876
(31) Kohyama, A.; Fukuda, M.; Sugiyama, S.; Yamakoshi, H.; Kanoh, N.; Ishioka, C.; Shibata, H.; Iwabuchi, Y., Reversibility of the thia-Michael reaction of cytotoxic C5-curcuminoid and structure-activity relationship of bis-thiol-adducts thereof. Org. Biomol. Chem. 2016, 14 (45), 10683–10687.
https://doi.org/10.1039/C6OB01771A
(32) Avonto, C.; Taglialatela-Scafati, O.; Pollastro, F.; Minassi, A.; Di Marzo, V.; De Petrocellis, L.; Appendino, G., An NMR spectroscopic method to identify and classify thiol-trapping agents: revival of Michael acceptors for drug discovery? Angew. Chem. Int. Ed. 2011, 50 (2), 467−471.
https://doi.org/10.1002/anie.201005959
(33) Amslinger, S.; Al-Rifai, N.; Winter, K.; Wormann, K.; Scholz, R.; Baumeister, P.; Wild, M., Reactivity assessment of chalcones by a kinetic thiol assay. Org. Biomol. Chem. 2013, 11 (4), 549–554.
https://doi.org/10.1039/C2OB27163J
(34) Qian, Y.; Zhong, P.; Liang, D.; Xu, Z.; Skibba, M.; Zeng, C.; Li, X.; Wei, T.; Wu, L.; Liang, G. A., Newly designed curcumin analog Y20 mitigates cardiac injury via anti-inflammatory and anti-oxidant actions in obese rats. PLoS One 2015, 10 (3), e0120215.
https://doi.org/10.1371/journal.pone.0120215
(35) Zhang, Y.; Pan, K.-L.; He, F.; Chen, L.-F.; Liu, Z.-G.; Liang, G., Crystal structure of (2E,6E)-2,6-bis[2-(trifluoromethyl)benzylidene]cyclohexanone, C22H16F6O. Zeitschrift für Kristallograhie – New Crystral Stuctures 2015, 230 (3), 271–272.
https://doi.org/10.1515/ncrs-2015-0009
(36) Liang, G.; Shao, L.; Wang, Y.; Zhao, C.; Chu, Y.; Xiao, J.; Zhao, Y.; Li, X.; Yang, S., Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorganic and Medicinal Chemistry 2009, 17 (6), 2623–2631. https://doi.org/ 10.1016/j.bmc.2008.10.044
(37) Kar, S.; Ramamoorthy, G.; Sinha, S.; Ramanan, M.; Pola, J. K.; Golakoti, N. R.; Nanubolu, J. B.; Sahoo, S. K.; Dandamudi, R. B.; Doble, M., Synthesis of diarylidenecyclohexanone derivatives as potential anti-inflammatory leads against COX-2/MPGES1 and 5-LOX. New J. Chem. 2019, 43 (23), 9012–9020. https://doi.org/10.1039/C9NJ00726A
(38) Ma, S. Y.; Zheng, Z. B.; Sun, Y. F.; Wang, Z. Y., (2E,6E)-2,6-difurfurylidenecyclohexanone. Acta Crystallogr. Sect. E Struct. Rep. Online 2009, 65 (12), o3085.
https://doi.org/10.1107/S160053680904728X
(39) Pinto, N.; Retailleau, P.; Voituriez, A.; Marinetti, A., Organocatalytic enantioselective desymmetrization of cyclic enonesviaphosphine promoted [3+2] annulations. Chem. Commun. 2011, 47 (3), 1015–1017.
https://doi.org/10.1039/C0CC03164J
(40) Liu, G.-Y.; Jia, C.-C.; Han, P.-R.; Yang, J., 3,5-Bis(2-fluorobenzylidene)-4-piperidone induce reactive oxygen species-mediated apoptosis in A549 cells. Med. Chem. Res. 2018, 27 (1), 128–136.
https://doi.org/10.1007/s00044-017-2056-x
(41) Bagiyan, G. A.; Koroleva, I. K.; Soroka, N. V.; Ufimtsev, A. V., Oxidation of Thiol compounds by molecular oxygen in aqueous solutions. Russ Chem Bull 2003, 52 (5), 1135–1141.
Downloads
Published
Versions
- 2023-07-01 (2)
- 2023-06-12 (1)
How to Cite
Issue
Section
License
Copyright (c) 2023 Zlatko Lozanovski, Jasmina Petreska Stanoeva, Jane Bogdanov
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors agree to the following licence: Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material
- for any purpose, even commercially.
Under the following terms:
Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- NonCommercial — You may not use the material for commercial purposes.
