Development of a spectrophotometric method for assessment of the relative reactivity of monocarbonyl analogs of curcumin with 2-(dimethylamino)ethanethiol

Authors

  • Zlatko Lozanovski Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje and Higher Medical School, St. Kliment Ohridski University in Bitola
  • Jasmina Petreska Stanoeva Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje https://orcid.org/0000-0003-0780-0660
  • Jane Bogdanov Institute of Chemistry, Faculty of Natural Sciences and Mathematics, Ss. Cyril and Methodius University in Skopje

DOI:

https://doi.org/10.20450/mjcce.2023.2638

Keywords:

synthesis, monocarbonyl analogs of curcumin, thiols, Michael addition, 2-(dimethylamino)ethanethiol

Abstract

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.

https://doi.org/10.1023/A:1024761324710

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Published

2023-06-12 — Updated on 2023-07-01

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How to Cite

Lozanovski, Z., Petreska Stanoeva, J., & Bogdanov, J. (2023). Development of a spectrophotometric method for assessment of the relative reactivity of monocarbonyl analogs of curcumin with 2-(dimethylamino)ethanethiol. Macedonian Journal of Chemistry and Chemical Engineering, 42(1), 13–24. https://doi.org/10.20450/mjcce.2023.2638 (Original work published June 12, 2023)

Issue

Vol. 42 No. 1 (2023)

Section

Organic Chemistry

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Copyright (c) 2023 Zlatko Lozanovski, Jasmina Petreska Stanoeva, Jane Bogdanov

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