Consensus-based comparison of chromatographic and computationally estimated lipophilicity of benzothiepino[3,2-c]pyridine derivatives as potential antifungal drugs
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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.
Keywords:
benzothiepino[3,2-c]pyridines / lipophilicity / multicriteria ranking / multivariate data analysis / sum of ranking differencesSource:
Journal of Separation Science, 2017, 40, 10, 2089-2096Publisher:
- Wiley-V C H Verlag Gmbh, Weinheim
Projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Structure-properties relationships of natural and synthetic molecules and their metal complexes (RS-172017)
Note:
- 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