Water-Soluble Heliomycin Derivatives to Target i-Motif DNA
| Autor: | Georgy Y Nadysev, George V. Zatonsky, Eugene E Bykov, Pin Ju Chueh, Zoë A. E. Waller, Alexander S. Tikhomirov, Andrey E. Shchekotikhin, Mahmoud A. S. Abdelhamid |
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| Rok vydání: | 2021 |
| Předmět: |
Scaffold
Pharmaceutical Science 01 natural sciences DNA sequencing Analytical Chemistry Cell Line chemistry.chemical_compound Mice Derivative (finance) Drug Discovery Side chain Animals Humans Polycyclic Compounds Pharmacology Natural product 010405 organic chemistry Organic Chemistry Water DNA Combinatorial chemistry 0104 chemical sciences G-Quadruplexes 010404 medicinal & biomolecular chemistry Complementary and alternative medicine chemistry Solubility Duplex (building) Molecular Medicine Nucleic Acid Conformation Selectivity |
| Zdroj: | Journal of natural products. 84(5) |
| ISSN: | 1520-6025 |
| Popis: | Heliomycin (also known as resistomycin) is an antibiotic with a broad spectrum of biological activities. However, low aqueous solubility and poor knowledge of its chemical properties have limited the development of this natural product. Here, we present an original scheme for the introduction of aminoalkylamine residues at positions 3, 5, and 7 of heliomycin and, using this, have prepared a series of novel water-soluble derivatives. The addition of side chains to the heliomycin scaffold significantly improves their interaction with different DNA secondary structures. One derivative, 7-deoxy-7-(2-aminoethyl)amino-10-O-methylheliomycin (8e), demonstrated affinity, stabilization potential, and good selectivity toward i-motif-forming DNA sequences over the duplex and G-quadruplex. Heliomycin derivatives therefore represent promising molecular scaffolds for further development as DNA-i-motif interacting ligands and potential chemotherapeutic agents. |
| Databáze: | OpenAIRE |
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