Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides dagger

0536266 - ÚVGZ 2021 RIV CH eng J - Článek v odborném periodiku
Kos, J. - Bak, A. - Kozik, V. - Jankech, T. - Strharsky, T. - Swietlicka, A. - Michnova, H. - Hošek, J. - Smolinski, A. - Oravec, Michal - Devinsky, F. - Hutta, M. - Jampílek, J.
Biological Activities and ADMET-Related Properties of Novel Set of Cinnamanilides dagger.
Molecules. Roč. 25, č. 18 (2020), č. článku 4121. E-ISSN 1420-3049
Grant CEP: GA MŠMT(CZ) EF16_019/0000797
Institucionální podpora: RVO:86652079
Klíčová slova: molecular lipophilicity * drug discovery * log-p * som-4d-qsar * prediction * hybrids * agents * pk(a) * dye * cinnamamides * synthesis * antistaphylococcal activity * MTT assay * cytotoxicity * lipophilicity * pca * ive-pls * quantitative structure-property relationships
Obor OECD: Demography
Impakt faktor: 4.412, rok: 2020
Způsob publikování: Open access
https://www.mdpi.com/1420-3049/25/18/4121

A series of nineteen novel ring-substitutedN-arylcinnamanilides was synthesized and characterized. All investigated compounds were tested againstStaphylococcus aureusas the reference strain, two clinical isolates of methicillin-resistantS. aureus(MRSA), andMycobacterium tuberculosis. (2E)-N-[3-Fluoro-4-(trifluoromethyl)phenyl]-3-phenylprop-2-enamide showed even better activity (minimum inhibitory concentration (MIC) 25.9 and 12.9 mu M) against MRSA isolates than the commonly used ampicillin (MIC 45.8 mu M). The screening of the cell viability was performed using THP1-Blue (TM) NF-kappa B cells and, except for (2E)-N-(4-bromo-3-chlorophenyl)-3-phenylprop-2-enamide (IC(50)6.5 mu M), none of the discussed compounds showed any significant cytotoxic effect up to 20 mu M. Moreover, all compounds were tested for their anti-inflammatory potential, several compounds attenuated the lipopolysaccharide-induced NF-kappa B activation and were more potent than the parental cinnamic acid. The lipophilicity values were specified experimentally as well. In addition, in silico approximation of the lipophilicity values was performed employing a set of free/commercial clogP estimators, corrected afterwards by the corresponding pK(a)calculated at physiological pH and subsequently cross-compared with the experimental parameters. The similarity-driven property space evaluation of structural analogs was carried out using the principal component analysis, Tanimoto metrics, and Kohonen mapping.
Trvalý link: http://hdl.handle.net/11104/0314080