1. Academic Validation
  2. Cytotoxic alpha-bromoacrylic derivatives of low molecular weight

Cytotoxic alpha-bromoacrylic derivatives of low molecular weight

  • Bioorg Med Chem Lett. 2002 Jun 3;12(11):1467-71. doi: 10.1016/s0960-894x(02)00177-4.
Italo Beria 1 Marina Caldarelli Cristina Geroni Nicola Mongelli Benedetta Reinach Luisella Vignati Paolo Cozzi
Affiliations

Affiliation

  • 1 Chemistry Department, Pharmacia Discovery Research Oncology, Viale Pasteur 10, 20014 Nerviano, Milan, Italy. italo.beria@pharmacia.com
Abstract

In vitro and in vivo activities of a small series of alpha-bromoacrylic derivatives of low molecular weight (MW) are described and compared with those of alpha-bromoacrylic derivatives of distamycin-like frames. Low MW compounds, when lacking of a strong basic moiety, are potent cytotoxics, while analogues bearing a strong basic moiety are not. This suggests the existence of an active transport mechanism for distamycin-derived cytotoxics characterized by strong basic amidino or guanidino moieties. Low MW compounds are inactive in vivo, possibly because of the metabolic lability of alpha-bromoacrylic moiety. The same moiety is however present in a series of potent Anticancer distamycin-like minor groove Binders, for example, PNU-166196 (brostallicin), a fact that underlines the features of the latter.

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