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Bis-daunomycin hydrazones: Interactions with DNA

Summary

A series of bis-daunomycin hydrazones were synthesised from diester diamide linking groups derived from α,ω-dicarboxylic acids. All members of the series bis-intercalated into DNA, as evidenced by doubling of the lengthening of rod-like DNA compared to daunomycin, and by a 1000–5000 fold slower dissociation from DNA than daunomycin under detergent sequestration conditions. The bis-hydrazones exhibited neighbour exclusion, and occupied 6 bp under saturating conditions of drug. A unique DNA sequence specificity was apparent from transcriptional footprinting of 100 bp of DNA, with the greatest preference for 5′-CACA sites.

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Correspondence to Don R. Phillips.

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Phillips, D.R., Brownlee, R.T.C., Reiss, J.A. et al. Bis-daunomycin hydrazones: Interactions with DNA. Invest New Drugs 10, 79–88 (1992). https://doi.org/10.1007/BF00873121

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Key words

  • bis-daunomycin hydrazones
  • DNA interaction
  • dissociation kinetics
  • DNA lengthening
  • DNA sequence selectivity
  • bis-intercalation