- Cytotoxic α-bromoacrylic derivatives of distamycin analogues modified at the amidino moiety
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The design, synthesis, in vitro and in vivo activities of novel α-bromoacrylic derivatives of distamycin A, modified at the amidino moiety by the replacement with basic or non-basic groups are reported. In spite of the relevance of these modifications of distamycin frame, the new derivatives are potent cytotoxics. The presence of the amidino moiety, is, therefore, not an absolute requirement for the activity. In particular due to a favorable myelotoxicity/cytotoxicity ratio, guanidino derivative PNU 166196 was selected for clinical development. (C) 2000 Elsevier Science Ltd. All rights reserved.
- Cozzi, Paolo,Beria, Italo,Caldarelli, Marina,Geroni, Cristina,Mongelli, Nicola,Pennella, Giulia
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- Process for preparing distamycin derivatives
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Compounds which are α-halogenoacryloyl distamycin derivatives of formula (I) wherein R1 is a bromine or chlorine atom; R2 is a distamycin or distamycin-like framework as set forth in the specification; or a pharmaceutically acceptable salt thereof; are cytotoxic agents particularly effective in the treatment of tumors over expressing GSH/GSTs system and which are poorly responsive or even resistant to conventional antitumor therapies.
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- Use of substituted acryloyl distamycin derivatives in the treatment of tumors associated with high levels of glutathione
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Compounds which are α-halogenoacryloyl distamycin derivatives of formula (I) wherein R1 is a bromine or chlorine atom; R2 is a distamycin or distamycin-like framework as set forth in the specification; or a pharmaceutically acceptable salt thereof; are cytotoxic agents particularly effective in the treatment of tumors over expressing GSH/GSTs system and which are poorly responsive or even resistant to conventional antitumor therapies.
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