Water-Soluble Heliomycin Derivatives to Target i-Motif DNA.

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.

Verification of oligomycin A structure: synthesis and biological evaluation of 33-dehydrooligomycin A.

Although, the structure of oligomycin A (1) was confirmed by spectroscopic and chemical evaluations, some crystallographic data cast doubt on the originally adopted structure of the side 2-hydroxypropyl moiety of this antibiotic. It was suggested that the side chain of the oligomycin is enol-related (2-hydroxy-1-propenyl). To clarify this matter we synthesized and evaluated 33-dehydrooligomycin A (2) prepared by the Kornblum oxidation of 33-O-mesyloligomycin A (3) by dimethyl sulfoxide. NMR data for 33-dehydrooligomycin (2) and results of quantum chemical calculations have shown that this derivative exists in the keto rather than in the enol tautomer 2a. The in vitro antimicrobial activity of 2 was approximately two times weaker in comparison with oligomycin A against Streptomyces fradiae ATCC-19609 and reference Candida spp. strains and similar activity against certain filamentous fungi. The docking binding estimate of 2 with FOF1ATP synthase showed a slight decrease in binding affinity for 2 when compared with oligomycin A; that correlated with its activity against S. fradiae ATCC 19609 that is supersensitive to oligomycin A. The in vitro antiproliferative activities of 2 are also discussed.