Modeling of the anticancer action for radical derivatives of nitroazoles: Quantitative Structure-Activity Relationship (QSAR) study

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Abstract

A QSAR analysis of the anti-tumor, anti-metastasis and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles (including metronidazole and hypoxic radiosensitizers RP-170, KU-2285 and sanazole (drug AK-2123)) and their nitro and nitroso anion radical derivatives against melanoma B16 in mice has been performed. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies and belongs to the group of "indirect" methods. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics accompany the geometrical requirements in the analysis of local 3D molecular similarity. By variation of weight coefficients for hydrophobicity, refraction increments, and partial charge it is possible to achieve better quality of QSAR and evaluate the importance of each characteristic for biological activity under consideration. It was found that hydrophobicity, molar refraction and charge characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Size and hydrophobic properties of substituents in nitro anion radicals play significant role for ligand-target interaction in the processes of inhibition of metastatic spreading and growth of metastatic colonies by nitroazoles. A scheme of competitive interaction of parent nitroazoles and their anion radicals with a target in organism is suggested. It can be concluded that the step of one-electron reduction of nitroazoles can be important for anticancer activity of these drugs.

Original languageEnglish
Pages (from-to)193-203
Number of pages11
JournalCancer Biotherapy and Radiopharmaceuticals
Volume17
Issue number2
Publication statusPublished - 2002
Externally publishedYes

Fingerprint

Quantitative Structure-Activity Relationship
Anions
Hydrophobic and Hydrophilic Interactions
Nitroso Compounds
Experimental Melanomas
Metronidazole
Pharmaceutical Preparations
Electrons
Neoplasm Metastasis
Ligands
Weights and Measures
Growth
Neoplasms

Keywords

  • Anti-tumor drugs
  • Nitroazoles
  • Quantitative structure-activity relationships
  • Radiosensitizers

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

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abstract = "A QSAR analysis of the anti-tumor, anti-metastasis and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles (including metronidazole and hypoxic radiosensitizers RP-170, KU-2285 and sanazole (drug AK-2123)) and their nitro and nitroso anion radical derivatives against melanoma B16 in mice has been performed. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies and belongs to the group of {"}indirect{"} methods. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics accompany the geometrical requirements in the analysis of local 3D molecular similarity. By variation of weight coefficients for hydrophobicity, refraction increments, and partial charge it is possible to achieve better quality of QSAR and evaluate the importance of each characteristic for biological activity under consideration. It was found that hydrophobicity, molar refraction and charge characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Size and hydrophobic properties of substituents in nitro anion radicals play significant role for ligand-target interaction in the processes of inhibition of metastatic spreading and growth of metastatic colonies by nitroazoles. A scheme of competitive interaction of parent nitroazoles and their anion radicals with a target in organism is suggested. It can be concluded that the step of one-electron reduction of nitroazoles can be important for anticancer activity of these drugs.",
keywords = "Anti-tumor drugs, Nitroazoles, Quantitative structure-activity relationships, Radiosensitizers",
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T1 - Modeling of the anticancer action for radical derivatives of nitroazoles

T2 - Quantitative Structure-Activity Relationship (QSAR) study

AU - Khlebnikov, Andrey Ivanovich

AU - Schepetkin, Igor

AU - Kwon, Byoung Se

PY - 2002

Y1 - 2002

N2 - A QSAR analysis of the anti-tumor, anti-metastasis and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles (including metronidazole and hypoxic radiosensitizers RP-170, KU-2285 and sanazole (drug AK-2123)) and their nitro and nitroso anion radical derivatives against melanoma B16 in mice has been performed. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies and belongs to the group of "indirect" methods. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics accompany the geometrical requirements in the analysis of local 3D molecular similarity. By variation of weight coefficients for hydrophobicity, refraction increments, and partial charge it is possible to achieve better quality of QSAR and evaluate the importance of each characteristic for biological activity under consideration. It was found that hydrophobicity, molar refraction and charge characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Size and hydrophobic properties of substituents in nitro anion radicals play significant role for ligand-target interaction in the processes of inhibition of metastatic spreading and growth of metastatic colonies by nitroazoles. A scheme of competitive interaction of parent nitroazoles and their anion radicals with a target in organism is suggested. It can be concluded that the step of one-electron reduction of nitroazoles can be important for anticancer activity of these drugs.

AB - A QSAR analysis of the anti-tumor, anti-metastasis and anti-colony formation (for metastatic colonies) activities of eighteen nitroazoles (including metronidazole and hypoxic radiosensitizers RP-170, KU-2285 and sanazole (drug AK-2123)) and their nitro and nitroso anion radical derivatives against melanoma B16 in mice has been performed. The QSAR models were built with the use of the frontal polygon method. This approach has features of different 3D QSAR methodologies and belongs to the group of "indirect" methods. The procedure allows to build robust models with high predictive ability even in series of diverse and conformationally flexible compounds. Key atomic characteristics accompany the geometrical requirements in the analysis of local 3D molecular similarity. By variation of weight coefficients for hydrophobicity, refraction increments, and partial charge it is possible to achieve better quality of QSAR and evaluate the importance of each characteristic for biological activity under consideration. It was found that hydrophobicity, molar refraction and charge characteristics of nitro anion radical derivatives are more significant for interaction with molecular targets than those of the parent compounds and of the nitroso anion radical derivatives. Size and hydrophobic properties of substituents in nitro anion radicals play significant role for ligand-target interaction in the processes of inhibition of metastatic spreading and growth of metastatic colonies by nitroazoles. A scheme of competitive interaction of parent nitroazoles and their anion radicals with a target in organism is suggested. It can be concluded that the step of one-electron reduction of nitroazoles can be important for anticancer activity of these drugs.

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