Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and adozelesin

P G Baraldi; B Cacciari; R Romagnoli; G Spalluto; R Gambari; N Bianchi; M Passadore; P Ambrosino; N Mongelli; P Cozzi; C Geroni

Synthesis, cytotoxicity, antitumor activity and sequence selective binding of two pyrazole analogs structurally related to the antitumor agents U-71,184 and adozelesin

Anticancer Drug Des. 1997 Oct;12(7):555-76.

Authors

P G Baraldi¹, B Cacciari, R Romagnoli, G Spalluto, R Gambari, N Bianchi, M Passadore, P Ambrosino, N Mongelli, P Cozzi, C Geroni

Affiliation

¹ Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Italy. [email protected]

PMID: 9365502

Abstract

Two pyrazole analogs structurally related to the antitumor agents adozelesin and U-71,184 respectively were synthesized. By using a polymerase chain reaction approach, both compounds show selective binding to A + T rich sequences exactly as reference compound U-71,184. In in vitro assays, against L1210 cell lines, both derivatives showed cytotoxicity in the pM range, values comparable with the natural target compound (+)-CC-1065. The most active compound showed very high antitumor activity in mice implanted with L1210 cells (ILS% 363).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / chemistry*
Benzofurans
Binding Sites
Cyclohexanecarboxylic Acids / chemistry*
Cyclohexenes
Duocarmycins
Indoles / chemistry*
Leukemia L1210 / pathology
Magnetic Resonance Spectroscopy
Mice
Neoplasm Transplantation
Polymerase Chain Reaction
Pyrazoles / chemical synthesis*
Pyrazoles / metabolism
Pyrazoles / pharmacology
Spectrophotometry, Infrared

Substances

Antineoplastic Agents
Benzofurans
Cyclohexanecarboxylic Acids
Cyclohexenes
Duocarmycins
Indoles
Pyrazoles
U 71184
adozelesin