Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential

Marko Jeremić; Jelena Dinić; Milica Pešić; Marija Stepanović; Irena Novaković; Dejan Šegan; Dušan Sladić

doi:10.2298/JSC180627062J

PDF (1,002 kB) Supplementary Material (3.87 MB)

Published: Dec 5, 2018

DOI: https://doi.org/10.2298/JSC180627062J

Keywords:

quinones anticancer activity multidrug resistant apoptosis antimicrobial activity cyclic voltammetry

Marko Jeremić

Innovation Center of the Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade

http://orcid.org/0000-0003-0205-948X

Jelena Dinić

Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade

http://orcid.org/0000-0003-3371-2381

Milica Pešić

Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade

http://orcid.org/0000-0002-9045-8239

Marija Stepanović

Institute for Biological Research "Siniša Stanković", University of Belgrade, Despota Stefana 142, 11060 Belgrade

Irena Novaković

Institute of Chemistry, Technology and Metallurgy, University of Belgrade, Center for Chemistry, Njegoševa 12, 11000 Belgrade

http://orcid.org/0000-0001-9881-1204

Dejan Šegan

Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade

http://orcid.org/0000-0003-1541-9106

Dušan Sladić

Faculty of Chemistry, University of Belgrade, Studentski trg 12–16, 11000 Belgrade

http://orcid.org/0000-0002-1000-9813

Abstract

In this paper, the synthesis of fourteen alkylamino and arylamino derivatives of sesquiterpene quinone avarone and its model compound tert-butylquinone is described. Branched, cyclic, allylic and benzylic alkylamino/arylamino groups were introduced into the quinone moiety. For all the obtained derivatives, their biological activity and redox properties were studied. The cytotoxic activity of the synthesized derivatives towards multidrug resistant (MDR) human non-small cell lung carcinoma NCI-H460/R cells, their sensitive counterpart NCI-H460 and human normal keratinocytes (HaCaT) was investigated. The antimicrobial activity towards Gram-positive and Gram-negative bacteria, and fungal cultures was determined. Some of the synthesized derivatives showed selectivity for cancer cells, including MDR cells. Regarding their cell death induction potential, the most promising compounds were allylamino derivatives, preferentially triggering apoptosis, with high selectivity for cancer cells, including MDR cells. Several compounds showed promising antimicrobial activity, comparable to those of commercial antibiotic and antimycotic agents.

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M. Jeremić, “Alkylamino and aralkylamino derivatives of avarone and its mimetic as selective agents against non-small cell lung cancer cells, their antibacterial and antifungal potential”, J. Serb. Chem. Soc., vol. 83, no. 11, pp. 1193–1207, Dec. 2018.

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Vol. 83 No. 11 (2018)

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Organic Chemistry

Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution license 4.0 that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.

References

GBD 2015 Mortality and Causes of Death Collaborators, Lancet 388 (2016) 1459

L. H. Kushi, C. Doyle, M. McCullough, C. L. Rock, W. Demark-Wahnefried, E. V. Bandera, S. Gapstur, A. V. Patel, K. Andrews, T. Gansler, Ca ̶ Cancer J. Clin. 62 (2012) 30

K. Mross, F. Kratz ,in Drug Delivery in Oncology: From Basic Research to Cancer Therapy, Vol. 1, F. Kratz, P. Senter, H. Steinhagen, Eds., Wiley–VCH, Weinheim, Germany, 2011, p. 3

K. Nooter, G. Stoter, Pathol., Res. Pract. 192 (1996) 768

M. González-Ibarra, N. Farfán, C. Trejo, S. Uribe, B. Lotina-Hennsen, J. Agric. Food Chem. 53 (2005) 3415

T.-S. Lin, L.-Y. Zhu, S.-P. Xu, A. A. Divo, A. C. Sartorelli, J. Med. Chem. 34 (1991) 1634

P. S. Sarin, D. Sun, A. Thornton, W. E. G. Müller, J. Natl. Cancer Inst. 78 (1987) 663

K. Müller, A. Sellmer, W. Wiergrebe, J. Nat. Prod. 62 (1999) 1134

A. J. M. da Silva, C. D. Netto, W. Pacienza-Lima, E. C. Torres-Santos, B. Rossi-Berg-man, S. Maurel, A. Valentin, P. R. R. Costa, J. Braz. Chem. Soc. 20 (2009) 176

L.-Y. Tao, J.-Y. Zhang, Y.-J. Liang, L.-M. Chen, L.-S. Zheng, F. Wang, Y.-J. Mi, Z.-G. She, K. K. W. To, Y.-C. Lin, L.-W. Fu, Mar. Drugs 8 (2010) 1094

V. Kuete, L. K. Omosa, V. R. Sipowo Tala, J. O. Midio, A. T. Mbaveng, S. Swaleh, O. Karaosmanoğlu, H. Sivas, BMC Pharmacol. Toxicol. 17 (2016) 60

R. R. Kitagawa, W. Vilegas, I. Z. Carlos, M. S. G. Raddi, Braz. J. Pharmacogn. 21 (2011) 1084

X. Wang, B. Thomas, R. Sachdeva, L. Arteburn, L. Frye, P. G. Hatcher, D. G. Cornwell, J. Ma, Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 3604

C. S. Coates, J. Ziegler, K. Manz, J. Good, B. Kang, S. Milikisiyants, R. Chatterjee, S. Hao, J. H. Golbeck, K. V. Lakshmi, J. Phys. Chem. B 117 (2013) 7210

G. Lenaz, M. L. Genova, Biochim. Biophys. Acta, Bioenerg. 1787 (2009) 563

M. G. Traber, J. F. Stevens, Free Radical Biol. Med. 51 (2011) 1000

A. Kijjoa, P. Sawangwong, Mar. Drugs 2 (2004) 73

T. F. Molinski, D. S. Dalisay, S. L. Lievens, J. P. Saludes, Nat. Rev. Drug Discovery 8 (2009) 69

M. Gordaliza, Mar. Drugs 8 (2010) 2849

M. Jeremić, M. Pešić, J. Dinić, J. Banković, I. Novaković, D. Šegan, D. Sladić, Eur. J. Med. Chem. 118 (2016) 107

J. Vilipić, I. Novaković, T. Stanojković, I. Matić, D. Šegan, Z. Kljajić, D. Sladić, Bioorg. Med. Chem. 23 (2015) 6930

National Cancer Institute (NCI). Available from: https://www.cancer.gov/about-cancer/treatment/drugs/lung (last accessed 2018/04/10).

E. White, D. R. Green, in The molecular basis of cancer, 4th ed., J. Mendelsohn, J. W. Gray, P. M. Howley, M. A. Israel, C. B. Thompson, Eds., Elsevier Saunders, Philadelphia, PA, USA, 2015, pp. 209

G. Kroemer, L. Galluzzi, P. Vandenabeele, J. Abrams, E. S. Alnemri, E. H. Baehrecke, M. V. Blagosklonny, W. S. El-Deiry, P. Goldstein, D. R. Green. M. Hengartner, R. A. Knight, S. Kumar, S. A. Lipton, W. Malorni, G. Nuñez, M. E. Peter, J. Tschopp, J. Yuan, M. Piacentini, B. Zhivotovsky, G. Melino, Cell Death Differ. 16 (2009) 3

S. Elmore, Toxicol. Pathol. 35 (2007) 495

K. L. Rock, H. Kono, Annu. Rev. Pathol. 3 (2008) 99

L. M. Coussens, Z. Werb, Nature 420 (2002) 860

P. J. Boor, R. M. Hysmith, Toxicology 44 (1987) 129

S. Toyokuni, K. Okamoto, J. Yodoi, H. Hiai, FEBS Lett. 358 (1995) 1.

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