Evaluating Chemical Structure Similarity as an Indicator of Cellular Growth Inhibition

Chemical variations of small compounds are commonly used to probe biological systems and potentially discover lead-like compounds with selective target activity. Molecular probes are either generated by synthesis or acquired through directed searches of commercially available compound libraries. The...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2006-01, Vol.46 (1), p.430-437
Main Authors: Wallqvist, Anders, Huang, Ruili, Thanki, Narmada, Covell, David G
Format: Article
Language:English
Subjects:
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biology
Cell Division - drug effects
Cell growth
Cells
Chemicals
Computer Simulation
Dose-Response Relationship, Drug
Molecular structure
Neoplasms - pathology
Structure-Activity Relationship
Tumors
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Summary:Chemical variations of small compounds are commonly used to probe biological systems and potentially discover lead-like compounds with selective target activity. Molecular probes are either generated by synthesis or acquired through directed searches of commercially available compound libraries. The data generated when testing the probes in various biological systems constitutes a structure/activity analysis. The ability to detect variations and classify biological responses requires the analysis of a compound in multiple assays. While the concept of a structure/activity relationship is straightforward, its implementation can vary considerably depending on the biological system under study and the probe library selected for testing. The analysis presented here will focus on the accumulated compound library used to screen for growth inhibition across the National Cancer Institute's panel of 60 tumor cells. The considerable chemical and biological diversity inherent in these data offers an opportunity to establish a quantifiable connection between chemical structure and biological activity. We find that the connection between structure and biological response is not symmetric, with biological response better at predicting chemical structure than vice versa. Structurally and functionally similar compounds can have distinguishable biological responses reflecting different mechanisms of action.
ISSN:1549-9596
1549-960X
DOI:10.1021/ci0501544