Cymantrenyl-nucleobases: Synthesis, anticancer, antitrypanosomal and antimicrobial activity studies
| Autor: | Katarzyna Jakubiec-Krześniak, Gracia Mendoza, Barbara Krawczyk, Dominik Szczukocki, Vanesa Andreu, Konrad Kowalski, Manuel Arruebo, Kamil Durka, Aneta Koceva-Chyła, Karolina Matczak, Damian Trzybiński, Krzysztof Kochel, Jolanta Solecka, Krzysztof Woźniak, Dietmar Steverding, Artur Jabłoński |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Drug Evaluation
Preclinical Pharmaceutical Science Apoptosis medicine.disease_cause 01 natural sciences Analytical Chemistry chemistry.chemical_compound antibacterial activity Staphylococcus epidermidis Drug Discovery antitrypanosomal activity biology Chemistry nucleobases Antimicrobial Trypanocidal Agents cymantrene bioorganometallics anticancer activity Anti-Bacterial Agents Chemistry (miscellaneous) Staphylococcus aureus Molecular Medicine Fluorouracil Growth inhibition Antibacterial activity Cell Survival Stereochemistry Trypanosoma brucei brucei Antineoplastic Agents Trypanosoma brucei 010402 general chemistry Article lcsh:QD241-441 Structure-Activity Relationship lcsh:Organic chemistry Cell Line Tumor Autophagy Escherichia coli Organometallic Compounds medicine Humans Physical and Theoretical Chemistry 010405 organic chemistry Adenine Organic Chemistry Uracil biology.organism_classification 0104 chemical sciences Oxidative Stress |
| Zdroj: | Zaguán. Repositorio Digital de la Universidad de Zaragoza instname Molecules; Volume 22; Issue 12; Pages: 2220 Molecules, Vol 22, Iss 12, p 2220 (2017) Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|