Towards an Improvement of Anticancer Activity of Benzyl Adenosine Analogs
| العنوان: | Towards an Improvement of Anticancer Activity of Benzyl Adenosine Analogs |
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| المؤلفون: | Manuela Grimaldi, Maurizio Bifulco, Maria Proto, Verdiana Covelli, Mohammad Firoznezhad, Rosario Randino, Anna Maria D'Ursi, Patrizia Gazzerro, Manuela Rodriquez, Veronica De Simone, Gianluca Matteoli |
| المساهمون: | Covelli, V., Grimaldi, M., Randino, R., Firoznezhad, M., Proto, M. C., De Simone, V., Matteoli, G., Gazzerro, P., Bifulco, M., D'Ursi, A. M., Rodriquez, M. |
| المصدر: | Molecules, Vol 26, Iss 7146, p 7146 (2021) Molecules; Volume 26; Issue 23; Pages: 7146 Molecules |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Colorectal cancer, FPPS, N6-benzyladenosine derivatives, Adenosine, Animals, Antineoplastic Agents, Apoptosis, Cell Proliferation, Cell Survival, Colorectal Neoplasms, Computer Simulation, Drug Screening Assays, Antitumor, Geranyltranstransferase, HCT116 Cells, Humans, Mevalonic Acid, Mice, Structure-Activity Relationship, User-Computer Interface, Chemistry, Multidisciplinary, FARNESYL DIPHOSPHATE SYNTHASE, Farnesyl pyrophosphate, Pharmaceutical Science, Drug Screening Assays, Analytical Chemistry, chemistry.chemical_compound, QD241-441, colorectal cancer, Drug Discovery, CYTOKININ, chemistry.chemical_classification, ATP synthase, biology, TRANSFER DIFFERENCE NMR, APOPTOSIS, Chemistry, N6-ISOPENTENYLADENOSINE, Biochemistry, Chemistry (miscellaneous), Physical Sciences, Molecular Medicine, Life Sciences & Biomedicine, medicine.drug, Biochemistry & Molecular Biology, NUCLEOSIDES, ISOPRENOID END-PRODUCT, Article, CELL-PROLIFERATION, Prenylation, In vivo, medicine, Viability assay, BIOLOGICAL EVALUATION, Physical and Theoretical Chemistry, Science & Technology, Organic Chemistry, Antitumor, In vitro, Enzyme, chemistry, biology.protein, LIGAND |
| الوصف: | N6-Isopentenyladenosine (i6A) is a naturally occurring modified nucleoside displaying in vitro and in vivo antiproliferative and pro-apoptotic properties. In our previous studies, including an in silico inverse virtual screening, NMR experiments and in vitro enzymatic assays, we demonstrated that i6A targeted farnesyl pyrophosphate synthase (FPPS), a key enzyme involved in the mevalonate (MVA) pathway and prenylation of downstream proteins, which are aberrant in several cancers. Following our interest in the anticancer effects of FPPS inhibition, we developed a panel of i6A derivatives bearing bulky aromatic moieties in the N6 position of adenosine. With the aim of clarifying molecular action of N6-benzyladenosine analogs on the FPPS enzyme inhibition and cellular toxicity and proliferation, herein we report the evaluation of the N6-benzyladenosine derivatives' (compounds 2a-m) effects on cell viability and proliferation on HCT116, DLD-1 (human) and MC38 (murine) colorectal cancer cells (CRC). We found that compounds 2, 2a and 2c showed a persistent antiproliferative effect on human CRC lines and compound 2f exerted a significant effect in impairing the prenylation of RAS and Rap-1A proteins, confirming that the antitumor activity of 2f was related to the ability to inhibit FPPS activity. ispartof: MOLECULES vol:26 issue:23 ispartof: location:Switzerland status: published |
| وصف الملف: | Electronic; application/pdf |
| تدمد: | 1420-3049 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd05b972cb880efd7575b524e110c2e6Test https://doi.org/10.3390/molecules26237146Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dd05b972cb880efd7575b524e110c2e6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14203049 |
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