Consensus-Based Pharmacophore Mapping for New Set of N-(disubstituted-phenyl)-3-hydroxyl-naphthalene-2-carboxamides

Autor: Hana Michnová, Šárka Pospíšilová, Tomas Gonec, Josef Jampilek, Adam Smoliński, Violetta Kozik, Alois Cizek, Andrzej Bak, Jiri Kos
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Steric effects
Methicillin-Resistant Staphylococcus aureus
IVE-PLS
Stereochemistry
medicine.drug_class
Substituent
Carboxamide
antitubercular activity
Microbial Sensitivity Tests
Naphthalenes
01 natural sciences
Catalysis
Article
Inorganic Chemistry
lcsh:Chemistry
03 medical and health sciences
chemistry.chemical_compound
Anti-Infective Agents
medicine
lipophilicity
MTT assay
MIC
Physical and Theoretical Chemistry
Molecular Biology
lcsh:QH301-705.5
Spectroscopy
Trifluoromethyl
010405 organic chemistry
Chemistry
Organic Chemistry
General Medicine
Mycobacterium tuberculosis
3. Good health
0104 chemical sciences
Computer Science Applications
030104 developmental biology
lcsh:Biology (General)
lcsh:QD1-999
hydroxynaphthalenecarboxamides
Functional group
Lipophilicity
CoMSA
VE-PLS
similarity-activity landscape index
Pharmacophore
antistaphylococcal activity
Zdroj: International Journal of Molecular Sciences, Vol 21, Iss 6583, p 6583 (2020)
International Journal of Molecular Sciences
Volume 21
Issue 18
ISSN: 1661-6596
1422-0067
Popis: 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-hydroxy- naphthalene-2-carboxamide showed submicromolar (MICs 0.16&ndash
0.68 µ
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 µ
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, different distribution of mono-halogenated carboxamide derivatives with the &ndash
CF3 substituent is accompanied by the increased activity profile. A symmetric matrix of Tanimoto coefficients 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 cliffs. 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.
Databáze: OpenAIRE
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