Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Lipophilicity is one of the essential properties influencing drug absorption, excretion and metabolism. It is used for screening viable drug candidates. Chromatographic behavior of thiepino[3,2-c: 6,7-c'] dipyridine and 16 benzothiepino[3,2-c] pyridine derivatives as potential antifungal drugs was studied using thin-layer chromatography under typical reversed-phase conditions and two microemulsion chromatographic systems. Seventeen chromatographic and nine in silico lipophilicity measures were estimated. They were compared by classical multivariate approaches: principal component analysis, hierarchical cluster analysis, and ranked and grouped by the non-parametricmethod-Sum of ranking differences. Two computational and two chromatographic descriptors from the typical reversed-phase conditions using acetone/ water mixtures emerged as the best candidates for lipophilicity estimation. The principal component scores related to typical reversed-phase conditions using dioxane/ water were ran...ked as statistically insignificant ( the worst). Microemulsion systems were positioned in between, performing worse than in silico estimates. Thiepine derivatives were ranked and grouped by sum of ranking differences, fusing multiple lipophilicity measures. In multicriteria maximization ranking, the compound substituted by phenyl group at position 8 was selected as the most lipophilic one. It is also the most active against Candida albicans. The ranking confirmed that introduction of phenyl core is essential for increasing the lipophilicity of the studied compounds.
Ključne reči:
benzothiepino[3,2-c]pyridines / lipophilicity / multicriteria ranking / multivariate data analysis / sum of ranking differencesIzvor:
Journal of Separation Science, 2017, 40, 10, 2089-2096Izdavač:
- Wiley-V C H Verlag Gmbh, Weinheim
Finansiranje / projekti:
- Sinteza aminohinolina i njihovih derivata kao antimalarika i inhibitora botulinum neurotoksina A (RS-172008)
- Korelacija strukture i osobina prirodnih i sintetičkih molekula i njihovih kompleksa sa metalima (RS-172017)
Napomena:
- This is the peer-reviewed version of the following article: Šegan, S.; Božinović, N.; Opsenica, I.; Andrić, F. Consensus-Based Comparison of Chromatographic and Computationally Estimated Lipophilicity of Benzothiepino3,2-cPyridine Derivatives as Potential Antifungal Drugs. Journal of Separation Science 2017, 40 (10), 2089–2096, https://dx.doi.org/10.1002/jssc.201601442
- http://cer.ihtm.bg.ac.rs/handle/123456789/2243
DOI: 10.1002/jssc.201601442
ISSN: 1615-9306
PubMed: 28322031
WoS: 000402140300001
Scopus: 2-s2.0-85018854422
Institucija/grupa
IHTMTY - JOUR AU - Šegan, Sandra AU - Bozinovic, Nina AU - Opsenica, Igor AU - Andrić, Filip PY - 2017 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2982 AB - Lipophilicity is one of the essential properties influencing drug absorption, excretion and metabolism. It is used for screening viable drug candidates. Chromatographic behavior of thiepino[3,2-c: 6,7-c'] dipyridine and 16 benzothiepino[3,2-c] pyridine derivatives as potential antifungal drugs was studied using thin-layer chromatography under typical reversed-phase conditions and two microemulsion chromatographic systems. Seventeen chromatographic and nine in silico lipophilicity measures were estimated. They were compared by classical multivariate approaches: principal component analysis, hierarchical cluster analysis, and ranked and grouped by the non-parametricmethod-Sum of ranking differences. Two computational and two chromatographic descriptors from the typical reversed-phase conditions using acetone/ water mixtures emerged as the best candidates for lipophilicity estimation. The principal component scores related to typical reversed-phase conditions using dioxane/ water were ranked as statistically insignificant ( the worst). Microemulsion systems were positioned in between, performing worse than in silico estimates. Thiepine derivatives were ranked and grouped by sum of ranking differences, fusing multiple lipophilicity measures. In multicriteria maximization ranking, the compound substituted by phenyl group at position 8 was selected as the most lipophilic one. It is also the most active against Candida albicans. The ranking confirmed that introduction of phenyl core is essential for increasing the lipophilicity of the studied compounds. PB - Wiley-V C H Verlag Gmbh, Weinheim T2 - Journal of Separation Science T1 - Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs VL - 40 IS - 10 SP - 2089 EP - 2096 DO - 10.1002/jssc.201601442 ER -
@article{ author = "Šegan, Sandra and Bozinovic, Nina and Opsenica, Igor and Andrić, Filip", year = "2017", abstract = "Lipophilicity is one of the essential properties influencing drug absorption, excretion and metabolism. It is used for screening viable drug candidates. Chromatographic behavior of thiepino[3,2-c: 6,7-c'] dipyridine and 16 benzothiepino[3,2-c] pyridine derivatives as potential antifungal drugs was studied using thin-layer chromatography under typical reversed-phase conditions and two microemulsion chromatographic systems. Seventeen chromatographic and nine in silico lipophilicity measures were estimated. They were compared by classical multivariate approaches: principal component analysis, hierarchical cluster analysis, and ranked and grouped by the non-parametricmethod-Sum of ranking differences. Two computational and two chromatographic descriptors from the typical reversed-phase conditions using acetone/ water mixtures emerged as the best candidates for lipophilicity estimation. The principal component scores related to typical reversed-phase conditions using dioxane/ water were ranked as statistically insignificant ( the worst). Microemulsion systems were positioned in between, performing worse than in silico estimates. Thiepine derivatives were ranked and grouped by sum of ranking differences, fusing multiple lipophilicity measures. In multicriteria maximization ranking, the compound substituted by phenyl group at position 8 was selected as the most lipophilic one. It is also the most active against Candida albicans. The ranking confirmed that introduction of phenyl core is essential for increasing the lipophilicity of the studied compounds.", publisher = "Wiley-V C H Verlag Gmbh, Weinheim", journal = "Journal of Separation Science", title = "Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs", volume = "40", number = "10", pages = "2089-2096", doi = "10.1002/jssc.201601442" }
Šegan, S., Bozinovic, N., Opsenica, I.,& Andrić, F.. (2017). Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs. in Journal of Separation Science Wiley-V C H Verlag Gmbh, Weinheim., 40(10), 2089-2096. https://doi.org/10.1002/jssc.201601442
Šegan S, Bozinovic N, Opsenica I, Andrić F. Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs. in Journal of Separation Science. 2017;40(10):2089-2096. doi:10.1002/jssc.201601442 .
Šegan, Sandra, Bozinovic, Nina, Opsenica, Igor, Andrić, Filip, "Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs" in Journal of Separation Science, 40, no. 10 (2017):2089-2096, https://doi.org/10.1002/jssc.201601442 . .