Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives
Само за регистроване кориснике
2013
Аутори
Šegan, Sandra B.Trifković, Jelena
Verbić, Tatjana
Opsenica, Dejan M.
Zlatović, Mario
Burnett, James C.
Šolaja, Bogdan A.
Milojković-Opsenica, Dušanka
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area...). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles.
Кључне речи:
1,7-Bis(aminoalkyl)-diazachrysene derivatives (1,7-DAAC) / Lipophilicity / Acidity constants / Quantitative structure-retention relationship (QSRR) / Quantitative structure-activity relationship (QSAR)Извор:
Journal of Pharmaceutical and Biomedical Analysis, 2013, 72, 231-239Издавач:
- Elsevier Science Bv, Amsterdam
Финансирање / пројекти:
- Синтеза аминохинолина и њихових деривата као антималарика и инхибитора ботулинум неуротоксина А (RS-MESTD-Basic Research (BR or ON)-172008)
- National Cancer Institute, National Institutes of Health (USA) [HHSN261200800001E]
- NATOs Public Diplomacy Division [SfP983638]
Напомена:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3477
DOI: 10.1016/j.jpba.2012.08.025
ISSN: 0731-7085
PubMed: 22985530
WoS: 000311819100033
Scopus: 2-s2.0-84869079937
Колекције
Институција/група
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Šegan, Sandra B. AU - Trifković, Jelena AU - Verbić, Tatjana AU - Opsenica, Dejan M. AU - Zlatović, Mario AU - Burnett, James C. AU - Šolaja, Bogdan A. AU - Milojković-Opsenica, Dušanka PY - 2013 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1555 AB - The physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles. PB - Elsevier Science Bv, Amsterdam T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives VL - 72 SP - 231 EP - 239 DO - 10.1016/j.jpba.2012.08.025 ER -
@article{ author = "Šegan, Sandra B. and Trifković, Jelena and Verbić, Tatjana and Opsenica, Dejan M. and Zlatović, Mario and Burnett, James C. and Šolaja, Bogdan A. and Milojković-Opsenica, Dušanka", year = "2013", abstract = "The physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles.", publisher = "Elsevier Science Bv, Amsterdam", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives", volume = "72", pages = "231-239", doi = "10.1016/j.jpba.2012.08.025" }
Šegan, S. B., Trifković, J., Verbić, T., Opsenica, D. M., Zlatović, M., Burnett, J. C., Šolaja, B. A.,& Milojković-Opsenica, D.. (2013). Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives. in Journal of Pharmaceutical and Biomedical Analysis Elsevier Science Bv, Amsterdam., 72, 231-239. https://doi.org/10.1016/j.jpba.2012.08.025
Šegan SB, Trifković J, Verbić T, Opsenica DM, Zlatović M, Burnett JC, Šolaja BA, Milojković-Opsenica D. Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2013;72:231-239. doi:10.1016/j.jpba.2012.08.025 .
Šegan, Sandra B., Trifković, Jelena, Verbić, Tatjana, Opsenica, Dejan M., Zlatović, Mario, Burnett, James C., Šolaja, Bogdan A., Milojković-Opsenica, Dušanka, "Correlation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 72 (2013):231-239, https://doi.org/10.1016/j.jpba.2012.08.025 . .