Structural requirements for inhibitors of poly(ADP-ribose) Polymerase (original) (raw)

Summary

The purpose of this study was to examine the structure/activity relationships of a series of substituted benzamides as poly(ADP-ribose) polymerase inhibitors. The experimental approach has involved the use of in vitro and in vivo assays in order to gather information either on the intrinsic activity of the benzamides or on the effect of various pharmacodynamic parameters on the activity in vivo. Although some discrepancies between the data obtained in vivo and in vitro were found in this study, results seem to indicate that most powerful inhibitors were characterized by acylation of the -NH2 function in the 3 position or by substitution in this same position with hydroxy or methoxy groups. The best inhibitors were not cytotoxic under these experimental conditions. Computed calculations of molecular electrostatic potential of these molecules were also performed and a good correlation was found between the similarity index and the experimental inhibitory activity.

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Abbreviations

ADP-Rib polymerase:

poly(ADP-ribose) polymerase

SSF:

strand scission factor

MEP:

molecular electrostatic potential

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Author notes

1. O. Cantoni & D. Higgins
   Present address: Computing Service, University of Glasgow, G128QQ, Glasgow, Scotland, UK

Authors and Affiliations

1. Istituto di Farmacologia e Farmacognosia and Centro di Farmacologia Oncologica Sperimentale, Università di Urbino, Pavia, Italy
   P. Sestili & F. Cattabeni
2. Istituto di Chimica Farmaceutica, Università di Urbino, Pavia, Italy
   G. Spadoni, C. Balsamini & E. Duranti
3. Istituto di Genetica Biochimica ed Evoluzionistica-CNR, Pavia, Italy
   I. Scovassi & O. Cantoni
4. Dept. of Chemistry, University of St. Andrews, St. Andrews, Fife, Scotland KY16 9ST, UK
   D. Higgins & C. Thomson

Authors

1. P. Sestili
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2. G. Spadoni
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3. C. Balsamini
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4. I. Scovassi
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5. F. Cattabeni
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6. E. Duranti
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7. O. Cantoni
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8. D. Higgins
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9. C. Thomson
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Sestili, P., Spadoni, G., Balsamini, C. et al. Structural requirements for inhibitors of poly(ADP-ribose) Polymerase.J Cancer Res Clin Oncol 116, 615–622 (1990). https://doi.org/10.1007/BF01637083

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• Received: 26 January 1990
• Accepted: 29 May 1990
• Issue Date: November 1990
• DOI: https://doi.org/10.1007/BF01637083

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