Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies
The synthesis of four cymantrene-5-fluorouracil derivatives (1–4) 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-a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/12/2220 |
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| author | Artur Jabłoński Karolina Matczak Aneta Koceva-Chyła Kamil Durka Dietmar Steverding Katarzyna Jakubiec-Krześniak Jolanta Solecka Damian Trzybiński Krzysztof Woźniak Vanesa Andreu Gracia Mendoza Manuel Arruebo Krzysztof Kochel Barbara Krawczyk Dominik Szczukocki Konrad Kowalski |
| author_facet | Artur Jabłoński Karolina Matczak Aneta Koceva-Chyła Kamil Durka Dietmar Steverding Katarzyna Jakubiec-Krześniak Jolanta Solecka Damian Trzybiński Krzysztof Woźniak Vanesa Andreu Gracia Mendoza Manuel Arruebo Krzysztof Kochel Barbara Krawczyk Dominik Szczukocki Konrad Kowalski |
| author_sort | Artur Jabłoński |
| collection | DOAJ |
| description | The synthesis of four cymantrene-5-fluorouracil derivatives (1–4) 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 1–6 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. |
| first_indexed | 2024-12-23T14:54:00Z |
| format | Article |
| id | doaj.art-414906ab60af4f29ab601488d8bcd1a9 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T14:54:00Z |
| publishDate | 2017-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-414906ab60af4f29ab601488d8bcd1a92022-12-21T17:42:49ZengMDPI AGMolecules1420-30492017-12-012212222010.3390/molecules22122220molecules22122220Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity StudiesArtur Jabłoński0Karolina Matczak1Aneta Koceva-Chyła2Kamil Durka3Dietmar Steverding4Katarzyna Jakubiec-Krześniak5Jolanta Solecka6Damian Trzybiński7Krzysztof Woźniak8Vanesa Andreu9Gracia Mendoza10Manuel Arruebo11Krzysztof Kochel12Barbara Krawczyk13Dominik Szczukocki14Konrad Kowalski15Department of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, PolandDepartment of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, PolandDepartment of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, PolandDepartment of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, PolandBob Champion Research & Education Building, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7UQ, UKNational Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warszawa, PolandNational Institute of Public Health-National Institute of Hygiene, Chocimska 24, 00-791 Warszawa, PolandBiological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Żwirki and Wigury 101, 02-089 Warszawa, PolandBiological and Chemical Research Centre, Department of Chemistry, University of Warsaw, Żwirki and Wigury 101, 02-089 Warszawa, PolandDepartment 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, SpainDepartment 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, SpainDepartment 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, SpainDepartment of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Łódź, Pomorska 141/143, 90-236 Łódź, PolandFaculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, PolandFaculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, PolandDepartment of Organic Chemistry, Faculty of Chemistry, University of Łódź, Tamka 12, 91-403 Łódź, PolandThe synthesis of four cymantrene-5-fluorouracil derivatives (1–4) 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 1–6 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.https://www.mdpi.com/1420-3049/22/12/2220cymantrenenucleobasesbioorganometallicsanticancer activityantitrypanosomal activityantibacterial activity |
| spellingShingle | Artur Jabłoński Karolina Matczak Aneta Koceva-Chyła Kamil Durka Dietmar Steverding Katarzyna Jakubiec-Krześniak Jolanta Solecka Damian Trzybiński Krzysztof Woźniak Vanesa Andreu Gracia Mendoza Manuel Arruebo Krzysztof Kochel Barbara Krawczyk Dominik Szczukocki Konrad Kowalski Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies Molecules cymantrene nucleobases bioorganometallics anticancer activity antitrypanosomal activity antibacterial activity |
| title | Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies |
| title_full | Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies |
| title_fullStr | Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies |
| title_full_unstemmed | Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies |
| title_short | Cymantrenyl-Nucleobases: Synthesis, Anticancer, Antitrypanosomal and Antimicrobial Activity Studies |
| title_sort | cymantrenyl nucleobases synthesis anticancer antitrypanosomal and antimicrobial activity studies |
| topic | cymantrene nucleobases bioorganometallics anticancer activity antitrypanosomal activity antibacterial activity |
| url | https://www.mdpi.com/1420-3049/22/12/2220 |
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