TY - JOUR
T1 - Synthesis and antibacterial activity of fused Mannich ketones
AU - Lóránd, Tamás
AU - Kocsis, Béla
AU - Sohár, Pál
AU - Nagy, Gergely
AU - József, Pál
AU - Kispál, Gyula
AU - László, Renáta
AU - Prókai, László
N1 - Funding Information:
The authors are indebted to Dr A.C. for measuring the NMR spectra. The authors are grateful for financial support to OTKA program (#T 030261 and T-29651) and FKFP program (FKFP-0200/2000) and thank G.N. for her technical assistance.
PY - 2002/10
Y1 - 2002/10
N2 - New Mannich ketones of fused bicyclic ketones as 1-indanones and 1-tetralones were prepared using the classical acid-catalysed Mannich reaction. Known members of this family were used in comparative biological tests. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, E. coli ReD31m4, Salmonella minnesota Re595, Shigella sonnei Re4350, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cytotoxicity of our new compounds was evaluated against HeLa cell line. Some compounds showed low cytotoxicity (56.738 nM mL-1 for 24, 47.497 nM mL-1 for 31 and 48.379 nM mL-1 for 26) and proved to be efficient antibacterial agents against the Gram-positive and partly against E. coli strains. Minimum inhibitory concentrations (MIC) changed in the range of 1.56->200 μg mL-1. The deep rough mutants showed (generally eight times) higher sensitivity toward the compounds than the smooth E. coli. Hence, the permeability of Gram-negative outer membrane can influence the MIC values of our compounds. A preliminary quantitative structure-activity relationship (QSAR) study indicated the maximum positive charge (MaxQ+) as the parameter that most significantly affected antibacterial activity against E. coli. In B. subtilis, the influence of a topological descriptor (first-order valence-connectivity index, XV1) was also revealed; however, other strains did not yield meaningful QSAR with the set of descriptors employed.
AB - New Mannich ketones of fused bicyclic ketones as 1-indanones and 1-tetralones were prepared using the classical acid-catalysed Mannich reaction. Known members of this family were used in comparative biological tests. Antibacterial activity of these new water-soluble compounds was reported against Pseudomonas aeruginosa, Escherichia coli, E. coli ReD31m4, Salmonella minnesota Re595, Shigella sonnei Re4350, Staphylococcus aureus, Staphylococcus saprophyticus, Micrococcus luteus and Bacillus subtilis standard strains. Human cytotoxicity of our new compounds was evaluated against HeLa cell line. Some compounds showed low cytotoxicity (56.738 nM mL-1 for 24, 47.497 nM mL-1 for 31 and 48.379 nM mL-1 for 26) and proved to be efficient antibacterial agents against the Gram-positive and partly against E. coli strains. Minimum inhibitory concentrations (MIC) changed in the range of 1.56->200 μg mL-1. The deep rough mutants showed (generally eight times) higher sensitivity toward the compounds than the smooth E. coli. Hence, the permeability of Gram-negative outer membrane can influence the MIC values of our compounds. A preliminary quantitative structure-activity relationship (QSAR) study indicated the maximum positive charge (MaxQ+) as the parameter that most significantly affected antibacterial activity against E. coli. In B. subtilis, the influence of a topological descriptor (first-order valence-connectivity index, XV1) was also revealed; however, other strains did not yield meaningful QSAR with the set of descriptors employed.
KW - Antibacterial activity
KW - Cytotoxicity
KW - Deep rough mutants
KW - Mannich ketone
KW - QSAR
UR - http://www.scopus.com/inward/record.url?scp=0036809072&partnerID=8YFLogxK
U2 - 10.1016/S0223-5234(02)01404-6
DO - 10.1016/S0223-5234(02)01404-6
M3 - Article
C2 - 12446038
AN - SCOPUS:0036809072
SN - 0223-5234
VL - 37
SP - 803
EP - 812
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 10
ER -