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Open AccessArticle

Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies

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Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland
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Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, Poland
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Bob Champion Research & Education Building, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UK
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National Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warszawa, Poland
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Biological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Żwirki and Wigury 101, 02-089 Warszawa, Poland
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Department of Chemical Engineering. Aragon Institute of Nanoscience (INA), University of Zaragoza, Campus Río Ebro-Edificio I+D, C/ Poeta Mariano Esquillor S/N, 50018 Zaragoza, Spain
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Networking Research Center on Bioengineering, Biomaterials and Nanomedicine, CIBER-BBN, 28029 Madrid, Spain
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Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, Poland
*
Author to whom correspondence should be addressed.
Molecules 2017, 22(12), 2220; https://doi.org/10.3390/molecules22122220
Received: 28 November 2017 / Revised: 11 December 2017 / Accepted: 12 December 2017 / Published: 14 December 2017
(This article belongs to the Section Organic Chemistry)
The synthesis of four cymantrene-5-fluorouracil derivatives (14) and two cymantrene-adenine derivatives (5 and 6) is reported. All of the compounds were characterized by spectroscopic methods and the crystal structure of two derivatives (1 and 6), together with the previously described cymantrene-adenine compound C was determined by X-ray crystallography. While the compounds 1 and 6 crystallized in the triclinic P-1 space group, compound C crystallized in the monoclinic P21/m space group. The newly synthesized compounds 16 were tested together with the two previously described cymantrene derivatives B and C for their in vitro antiproliferative activity against seven cancer cell lines (MCF-7, MCF-7/DX, MDA-MB-231, SKOV-3, A549, HepG2m and U-87-MG), five bacterial strains Staphylococcus aureus (methicillin-sensitive, methicillin-resistant and vancomycin-intermediate strains), Staphylococcus epidermidis, and Escherichia coli, including clinical isolates of S. aureus and S. epidermidis, as well as against the protozoan parasite Trypanosoma brucei. The most cytotoxic compounds were derivatives 2 and C for A549 and SKOV-3 cancer cell lines, respectively, with 50% growth inhibition (IC50) values of about 7 µM. The anticancer activity of the cymantrene compounds was determined to be due to their ability to induce oxidative stress and to trigger apoptosis and autophagy in cancer cells. Three derivatives (1, 4 and 5) displayed promising antitrypanosomal activity, with GI50 values in the low micromolar range (3–4 µM). The introduction of the 5-fluorouracil moiety in 1 enhanced the trypanocidal activity when compared to the activity previously reported for the corresponding uracil derivative. The antibacterial activity of cymantrene compounds 1 and C was within the range of 8–64 µg/mL and seemed to be the result of induced cell shrinking. View Full-Text
Keywords: cymantrene; nucleobases; bioorganometallics; anticancer activity; antitrypanosomal activity; antibacterial activity cymantrene; nucleobases; bioorganometallics; anticancer activity; antitrypanosomal activity; antibacterial activity
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MDPI and ACS Style

Jabłoński, A.; Matczak, K.; Koceva-Chyła, A.; Durka, K.; Steverding, D.; Jakubiec-Krześniak, K.; Solecka, J.; Trzybiński, D.; Woźniak, K.; Andreu, V.; Mendoza, G.; Arruebo, M.; Kochel, K.; Krawczyk, B.; Szczukocki, D.; Kowalski, K. Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies. Molecules 2017, 22, 2220.

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