Tikhomirov Alexander S, Abdelhamid Mahmoud A S, Nadysev Georgy Y, Zatonsky George V, Bykov Eugene E, Chueh Pin Ju, Waller Zoë A E, Shchekotikhin Andrey E
Laboratory of Chemical Transformation of Antibiotics, Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, Moscow 119021, Russia.
Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
J Nat Prod. 2021 May 28;84(5):1617-1625. doi: 10.1021/acs.jnatprod.1c00162. Epub 2021 May 11.
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--methylheliomycin (), 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.
日光霉素（也称为抗霉素）是一种具有广泛生物活性的抗生素。然而，其低水溶性以及对其化学性质了解不足限制了这种天然产物的开发。在此，我们提出了一种在日光霉素的3、5和7位引入氨基烷基胺残基的原创方案，并据此制备了一系列新型水溶性衍生物。在日光霉素骨架上添加侧链显著改善了它们与不同DNA二级结构的相互作用。一种衍生物，7-脱氧-7-(2-氨基乙基)氨基-10-甲基日光霉素（），对形成i-基序的DNA序列表现出亲和力、稳定潜力，并且相对于双链体和G-四链体具有良好的选择性。因此，日光霉素衍生物是作为DNA-i-基序相互作用配体和潜在化疗药物进一步开发的有前景的分子骨架。
