1. Academic Validation
  2. Water-Soluble Heliomycin Derivatives to Target i-Motif DNA

Water-Soluble Heliomycin Derivatives to Target i-Motif DNA

  • J Nat Prod. 2021 May 28;84(5):1617-1625. doi: 10.1021/acs.jnatprod.1c00162.
Alexander S Tikhomirov 1 Mahmoud A S Abdelhamid 2 Georgy Y Nadysev 1 George V Zatonsky 1 Eugene E Bykov 1 Pin Ju Chueh 3 Zoë A E Waller 4 Andrey E Shchekotikhin 1
Affiliations

Affiliations

  • 1 Laboratory of Chemical Transformation of Antibiotics, Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, Moscow 119021, Russia.
  • 2 Department of Chemistry, University of Sheffield, Sheffield S3 7HF, United Kingdom.
  • 3 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan, Republic of China.
  • 4 School of Pharmacy, University College London, 29-39 Brunswick Square, London WC1N 1AX, United Kingdom.
Abstract

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.

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