http://hdl.handle.net/20.500.12128/15968
Title: | Consensus-based pharmacophore mapping for new set of N-(disubstitutedphenyl)- 3-hydroxyl-naphthalene-2-carboxamides |
Authors: | Bąk, Andrzej Kos, Jiri Michnova, Hana Gonec, Tomas Pospisilova, Sarka Kozik, Violetta Cizek, Alois Smoliński, Adam Jampilek, Josef |
Keywords: | hydroxynaphthalenecarboxamides; lipophilicity; antistaphylococcal activity; antitubercular activity; MIC; MTT assay; CoMSA; VE-PLS; similarity-activity landscape index |
Issue Date: | 2020 |
Citation: | "International Journal of Molecular Sciences" (2020) Iss. 18, art. no. 6583 |
Abstract: | A series of twenty-two novel N-(disubstituted-phenyl)-3-hydroxynaphthalene- 2-carboxamide derivatives was synthesized and characterized as potential antimicrobial agents. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[2-chloro-5-(trifluoromethyl)phenyl]-3-hydroxynaphthalene- 2-carboxamide showed submicromolar (MICs 0.16–0.68 M) activity against methicillin-resistant Staphylococcus aureus isolates. N-[3,5-bis(trifluoromethyl)phenyl]- and N-[4-bromo-3-(trifluoromethyl)phenyl]-3-hydroxynaphthalene-2-carboxamide revealed activity against M. tuberculosis (both MICs 10 M) comparable with that of rifampicin. Synergistic activity was observed for the combinations of ciprofloxacin with N-[4-bromo-3-(trifluoromethyl)phenyl]- and N-(4-bromo-3-fluorophenyl)-3-hydroxynaphthalene-2-carboxamides against MRSA SA 630 isolate. The similarity-related property space assessment for the congeneric series of structurally related carboxamide derivatives was performed using the principal component analysis. Interestingly, di erent distribution of mono-halogenated carboxamide derivatives with the –CF3 substituent is accompanied by the increased activity profile. A symmetric matrix of Tanimoto coe cients indicated the structural dissimilarities of dichloro- and dimetoxy-substituted isomers from the remaining ones. Moreover, the quantitative sampling of similarity-related activity landscape provided a subtle picture of favorable and disallowed structural modifications that are valid for determining activity cli s. Finally, the advanced method of neural network quantitative SAR was engaged to illustrate the key 3D steric/electronic/lipophilic features of the ligand-site composition by the systematic probing of the functional group. |
URI: | http://hdl.handle.net/20.500.12128/15968 |
DOI: | 10.3390/ijms21186583 |
ISSN: | 1422-0067 |
Appears in Collections: | Artykuły (WNŚiT) |
File | Description | Size | Format | |
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Bak_Kozik_consensus_based_pharmacophore_mapping.pdf | 1,58 MB | Adobe PDF | View/Open |
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