DNA minor groove binders

Design of DNA minor-groove binders as new antitumor agents 99F15. 

The DNA minor groove binder brostallicin (PNU-166196, 24), currently in Phase 2 clinical trials for the treatment of soft-tissue sarcoma, exhibited potent... 

Scheme 2.2-9. C2Bio-containing DNA minor groove binders. 

Carteau S, Mouscadet JF, Goulaouic H, Subra F, Auclair C. Inhibition of the in vitro integration of Moloney murine leukemia virus DNA by the DNA minor groove binder netropsin. Biochem Pharmacol... 

Design, synthesis, and biological evaluation of DNA minor-groove binders, ligands structurally related to CC-1065, distamycin, and anthramycin 03PAC187. 

Imidates derived from nitriles and alcohols are also effective precursors for the preparation of amidines. For example, furamidine, known as an active compound towards parasitic microorganisms and DNA minor groove binder [22], and its derivative DB-181, were synthesized from nitrile via the corresponding imidate [23] (Scheme 3.9). 

T. Ueda, S. Kakunaga, M. Ando, K. Yonemori, H. Sugiura, K. Yamada, and A. Kawai, Phase 1 and pharmacokinetic study of trabectedin, a DNA minor groove binder, administered as a 24-h continuous infusion in Japanese patients with soft tissue sarcoma. Invest. New Drugs, (2014). 

In this section we shall briefly review the solution of the energy decomposition problem for various types of NA binding drags, viz. DNA aromatic intercalators, DNA minor groove binders (or MGB-ligands), RNA aptamer binders. 

Energy analysis of ligand-NA interactions, sketched out above for typical DNA in-tercalators, DNA minor groove binders and RNA binders, enables us to answer the key question, viz. What physical factors stabilize/destabilize the ligand-NA complexes in solution and what are their relative importance The follow-up question now is How one can use the results of the energy analysis, say, in rational design of new drags ... 

Cai X, Gray PJ, Von Holf DD (2009) DNA minor groove binders back in the groove. Cancer Treatment Rev 35(5) 437-450... 

For review of distamycin and netropsin analogues Bailly, C. and Chaires, J. B. (1998) Sequence-specific DNA minor groove binders. Design and synthesis of netropsin and distamycin analogues. Bioconjugate Chem. 9,513-538. 

R. D. DNA binding compounds. VI. Synthesis and characterization of 2,5 -disubstituted bibenzimidazoles related to the DNA minor groove binder Hoechst 33258. Aust. J. Chem. 1994, 47, 1751-1769. 

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