Distamycin analogues

Cozzi P, Beria 1, Caldarelli M, Geroni C, Mongelli N, Pennella G. (2000) Cytotoxic alpha-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety. Bioorg Med Chem Lett 10 1273-1276. 

Since activated Cu(3-Clip-Phen) cleaves DNA without clear sequence selectivity it is the ability of the copper complex of the conjugate of 3-Clip-Phen with the distamycin analogue to produce, after activation, sequence selective DNA cleavage that allowed easier confirmation of these... 

Pitie M, Burrows CJ, Meunier B. Mechanisms of DNA cleavage by copper complexes of 3-CHp-Phen and of its conjugate with a distamycin analogue. Nucleic Acids Res. 2000 28 4856-4864. 

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. 

Lombardi, P. and A. Crisanti. Antima-larial activity of synthetic analogues of distamycin. Pharmacol. Then 1997, 76, 125-133. 

Synthetic analogues of distamycin A may be divided into two major classes. 

To the first class belong those analogues which, unmodified in the side chain, contain a different number of residues of 4-amino-l-methylpyrrole-2-carboxylic, acid. In the second class are considered those analogues which show modifications in side chains of the distamycin molecule. These modifications have been achieved either in the propionamidine side chain, or in the formyl-amino side chain. These analogues have been synthesized by Arcamone et a .25, 26). 

Fig. 6. Distamycin A analogues with different number of pyrrole residues...

Table 6. Inhibition of DNA-polymerase activity of FL virions by distamycin A and its analogues in the presence of various templates. Figures in brackets are percentages...

Fig. 12. Analogues of distamycin A with side chain modifications...

Table 1 3. Inhibition of DNA-dependent DNA polymerase reaction (E. coli B) by distamycin A and its structural analogues...

In the search for simpler analogues of netropsine and distamycin A, which are DNA minor groove binding antibiotics, pyrazoles (316) and (317) have been synthesized <89JOC428). The x-ray structure of (316) was reported. 

Koppel, L, Koppel, J. and Leito, I. (1996) Basicity of 3-aminopropionamidine derivatives in water and dimethyl sulphoxide. impheation for a pivotal step in the synthesis of distamycin A analogues. Journal of Physical Organic Chemistry, 9, 265-268. 

A number of synthetic analogues of distamycin and netropsin have been found to have excellent antitumor activity. For example, FCE 24517 (41), which is a nitrogen mustard-distamycin hybrid, is in clinical trials . The distamycin derivative (42) has increased water solubihty and enhanced cellular uptake <95H(4l)337>, and (43) is one of several related antitumor compounds with... 

---