Synthesis and Antiproliferative Activity of Marine Bromotyrosine Purpurealidin I and Its Derivatives
| Autor: | Manuela Voráčová, Katja-Emilia Lillsunde, Polina Ilina, Irene Tilli, Eero Mäki-Lohiluoma, Heinrich Lang, Tanja Bruun, Chinmay Bhat, Nives Hribernik, Jari Yli-Kauhaluoma, Victoria Barba, Paula Kiuru, Päivi Tammela, Tobias Rüffer |
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| Přispěvatelé: | Bioactivity Screening Group, Division of Pharmaceutical Biosciences, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, Drug Research Program, Pharmaceutical Design and Discovery group, Jari Yli-Kauhaluoma / Principal Investigator |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Aquatic Organisms
synthesis Pyridines selectivity to cancer cells education Pharmaceutical Science Antineoplastic Agents 010402 general chemistry 01 natural sciences Article Structure-Activity Relationship chemistry.chemical_compound Drug Development Cell Line Tumor Drug Discovery medicine Animals Humans Moiety bromotyrosines Cytotoxicity Fibroblast Pseudoceratina purpurea Pharmacology Toxicology and Pharmaceutics (miscellaneous) lcsh:QH301-705.5 Molecular Structure 010405 organic chemistry Total synthesis Fibroblasts Tyramine Purpurealidin I Combinatorial chemistry Porifera 0104 chemical sciences 3. Good health medicine.anatomical_structure chemistry lcsh:Biology (General) 317 Pharmacy Melanoma cell line Tyrosine cytotoxicity Drug Screening Assays Antitumor Normal skin Selectivity |
| Zdroj: | Marine Drugs Volume 16 Issue 12 Marine Drugs, Vol 16, Iss 12, p 481 (2018) |
| ISSN: | 1660-3397 |
| DOI: | 10.3390/md16120481 |
| Popis: | The first total synthesis of the marine bromotyrosine purpurealidin I (1) using trifluoroacetoxy protection group and its dimethylated analog (29) is reported along with 16 simplified bromotyrosine derivatives lacking the tyramine moiety. Their cytotoxicity was evaluated against the human malignant melanoma cell line (A-375) and normal skin fibroblast cells (Hs27) together with 33 purpurealidin-inspired simplified amides, and the structure&ndash activity relationships were investigated. The synthesized simplified analogs without the tyramine part retained the cytotoxic activity. Purpurealidin I (1) showed no selectivity but its simplified pyridin-2-yl derivative (36) had the best improvement in selectivity (Selectivity index 4.1). This shows that the marine bromotyrosines are promising scaffolds for developing cytotoxic agents and the full understanding of the elements of their SAR and improving the selectivity requires further optimization of simplified bromotyrosine derivatives. |
| Databáze: | OpenAIRE |
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