Structure activity relationships: their function in biological prediction

Conference · Thu Dec 31 23:00:00 EST 1981

OSTI ID:5544773

Schultz, T W

Quantitative structure activity relationships provide a means of ranking or predicting biological effects based on chemical structure. For each compound used to formulate a structure activity model two kinds of quantitative information are required: (1) biological activity and (2) molecular properties. Molecular properties are of three types: (1) molecular shape, (2) physiochemical parameters, and (3) abstract quantitations of molecular structure. Currently the two best descriptors are the hydrophobic parameter, log 1-octanol/water partition coefficient (log P), and the /sup 1/X/sup v/(one-chi-v) molecular connectivity index. Biological responses can be divided into three main categories: (1) non-specific effects due to membrane perturbation, (2) non-specific effects due to interaction with functional groups of proteins, and (3) specific effects due to interaction with receptors. Twenty-six synthetic fossil fuel-related nitrogen-containing aromatic compounds were examined to determine the quantitative correlation between log P and /sup 1/X/sup v/ and population growth impairment of Tetrahymena pyriformis. Nitro-containing compounds are the most active, followed by amino-containing compounds and azaarenes. Within each analog series activity increases with alkyl substitution and ring addition. The planar model log BR = 0.5564 log P + 0.3000 /sup 1/X/sup v/ -2.0138 was determined using mono-nitrogen substituted compounds. Attempts to extrapolate this model to dinitrogen-containing molecules were, for the most part, unsuccessful because of a change in mode of action from membrane perturbation to uncoupling of oxidative phosphoralation.

• Research Organization: Oak Ridge National Lab., TN (USA); Tennessee Univ., Knoxville (USA). Dept. of Animal Science; Virginia Commonwealth Univ., Richmond (USA). Dept. of Pharmaceutical Chemistry
• DOE Contract Number: W-7405-ENG-26
• OSTI ID: 5544773
• Report Number(s): CONF-821048-3; ON: DE84001997
• Country of Publication: United States
• Language: English

Related Subjects

560302* -- Chemicals Metabolism & Toxicology-- Microorganisms-- (-1987)
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ACRIDINES
AMINES
ANILINE
ANIMALS
AROMATICS
AZAARENES
AZINES
BIOASSAY
BIOLOGICAL EFFECTS
CILIATA
DOSE-RESPONSE RELATIONSHIPS
ENERGY SOURCES
FOSSIL FUELS
FUELS
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INVERTEBRATES
MATHEMATICAL MODELS
MICROORGANISMS
MOLECULAR STRUCTURE
NITRO COMPOUNDS
NITROBENZENE
NITROPHENOL
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHENOLS
PICOLINES
PROTOZOA
PYRAZINES
PYRIDINE
PYRIDINES
QUINOLINES
TETRAHYMENA
TOLUIDINES
TOXICITY