Mutagenicity structure-activity relationship

Enslein, K. An overview of structure-activity relationships as an alternative to testing in animals for carcinogenicity, mutagenicity, dermal and eye irritation, and acute oral toxicity. Toxicol Industrial Health 1988 4 479-98. 

Benigni R, Giuliani A. Quantitative structure-activity relationship (QSAR) studies of mutagens and carcinogens. Med Res Rev 1996 16 267-84. 

Debnath AK, Lopez de Compadre RL, Debnath G, Shusterman AJ, Hansch C. Structure-activity relationship of mutagenic aromatic and heteroaromatic nitrocompounds—correlation with molecular orbital energies and hydrophobicity. I Med Chem 1991 34 786-97. 

The Danish EPA has developed an advisory list for self-classification of dangerous substances including 20 624 substances. The substances have been identified by means of QSAR models (Quantitative Structure-Activity Relationship) as having acute oral toxicity, sensitization, mutagenicity, carcinogenicity, and/or danger to the aquatic environment. 

Helma C (2006) Lazy structure-activity relationships (lazar) for the prediction of rodent carcinogenicity and salmonella mutagenicity. Mol Divers 10 147-158... 

Chung KT, Cemiglia CE (1992) Mutagenicity of azo dyes structure-activity relationships. Mut Res 277 201-220... 

A hierarchical approach. In Quantitative Structure-Activity Relationship (QSAR) Models of Mutagens and Carcinogens, Benigni, R., Ed., CRC Press, Boca Raton, FL, 2003, pp. 207-234. 

Basak, S. C., Gute, B. D., Grunwald, G. D. Relative effectiveness of topological, geometrical, and quantum chemical parameters in estimating mutagenicity of chemicals. In Quantitative Structure—Activity Relationships in Environmental Sciences VII, Chen, F., Schuurmann, G., Eds., SETAC Press, Pensacola, EL, 1998, pp. 245-261. 

Frierson, M.R., Klopman, G., and Rosenkranz, H.S. (1986). Structure-activity relationships (SARs) among mutagens and carcinogens A review. Env. Mutagen. 8 283-327. 

WIN 57294 137 is a potent inhibitor of DNA gyrase it is both clastogenic and mutagenic, which precluded its development as a human anti-infective agent [193]. This compound was subsequently found to possess moderate topo II inhibitory activity ( 50=7.6 pM). Structure activity relationship studies of WIN 57294 137 resulted in the discovery that the 3-CO2H group was not a requisite for topo II potency for 138, ( 50= 17 pM) [194]. A conformationally rigid quinolone derivative 139 has been reported to display better topo II potency ( 50=2.77 pM) [195]. 

Spanggord RJ, Mortelmans KE, Griffin AF, et al. 1982b. Mutagenicity in Salmonella typhimurium and structure-activity relationships of wastewater components emanating from the manufacture of trinitrotoluene. Environ Mutagen 4 163-179. 

Lewis, D. F., Ioannides, C., and Parke, D. V. (2003) A quantitative structure-activity relationship (QSAR) study of mutagenicity in several series of organic... 

Mermelstein, R., E. C. McCoy, and H. S. Rosenkranz, The Mutagenic Properties of Nitroarenes Structure-Activity Relationships, in Toxicity of Nitroarenes (D. E. Rickert, Ed.), Chap. 14, Hemisphere Publishing, Washington, DC, 1985. 

Patlewicz, G., Rodford, R. and Walker, J.D. (2003) Quantitative structure-activity relationships for predicting mutagenicity and carcinogenicity. Environ. Toxicol. Chem., 22 (8),... 

Dawson, D.A., Schultz, T.W. and Hunter, R.S. (1996) Developmental toxicity of carboxylic acids to Xenopus embryos a quantitative structure-activity relationship and computer-automated structure evaluation. Teratog Carcinog Mutagen, 16, 109-124. 

Benigni, R., Andreoli, C. and Giuliani, A. (1989) Quantitative structure—activity relationships principles and applications to mutagenicity and carcinogenicity. Mutat. Res., 221, 197—216. 

Woo, Y.-T. (1983) Carcinogenicity, mutagenicity and teratogenicity of carbamates, fhiocarbamates and related compounds an overview of structure-activity relationships and environmental concerns. Environ. Carcinog. Ecotoxicol. Rev., Cl (1), 97-133. 

Blake BW, Enslein K, Gombar VK, et al. 1990. Salmonella mutagenicity and rodent carcinogenicity quantitative structure-activity relationships. Mutat Res 241(3) 261-271. 

Neudecker, T., Lutz, D., Eder, E. Henschler, D. (1980) Structure-activity relationship in halogen and alkyl substituted allyl and allylic compounds correlation of alkylating and mutagenic properties. Biochem. Pharmacol.. 29, 2611-2617... 

In addition to structure-activity relationships, dozens of useful tests have been developed for mutagenicity to germ cells and somatic cells and inferred carcinogenicity. The most straightforward means of testing for effects on DNA is an examination of DNA itself. This is normally difficult to do, so indirect tests are used. One useful test measures the activity of DNA repair mechanisms (unscheduled DNA synthesis) a higher activity is indicative of prior damage to DNA. 

Figure 8.4 Functionalities commonly associated with genotoxicity and mutagenicity. These groups are used in structure-activity relationships to alert for possible carcinogenic substances.

Debnath, A.K., Hansch, C. (1992) Structure-activity relationship of genotoxic polycyclic aromatic nitro compounds. Further evidence for the importance of hydrophobicity and molecular orbital energies in genetic toxicity. Environ. Mol. Mutagen. 20, 140-144. 

W.A. Vance et al., Disubstituted amino-, nitroso-, and nitrofluorenes A physicochemical basis for structure-activity relationships in Salmonella typhimurium. Environ. Mutagen. 9, 123-141 (1987)... 

R. Benigni, Structure-activity relationship studies of chemical mutagens and carcinogens Mechanistic investigations and prediction approaches. Chem. Rev. 105, 1767-1800 (2005)... 

D.B. Walsh, L.D. Claxton, Computer-assisted structure-activity relationships of nitrogenous cyclic compounds tested in Salmonella assays for mutagenicity. Mutat. Res. 182, 55-64 (1987)... 

A.K. Debnath et al., Quantitative structure-activity relationship investigation of the role of hydrophobicity in regulating mutagenicity in the Ames test 2 Mutagenicity of aromatic and heteroaromatic nitro compounds in Salmonella typhimurium TA100. Environ. Mol. Mutagen. 19, 53-70 (1992)... 

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