p-Guanidinoethyl calixarene and parent phenol derivatives exhibiting antibacterial activities. Synthesis and biological evaluation.
The tetra-para-guanidinoethyl-calix[4]arene, its distally-disubstituted ether derivatives involving 2,2'-bithiazolyl- or 2,2'-bipyridyl-methyl groups, as well as the para-guanidinoethylphenol and its analogous derivatives have been synthesized, fully characterized and evaluated as antibacterial agents towards both gram positive and gram negative reference bacteria. The simple phenolic species showed lower activity than their calixarene analogues, confirming the hypothesis that a synergistic effect should result from the spatial organization of guanidinium and heterocycles on a macrocyclic scaffold. Introduction of the bithiazole and bipyridine substituents enhanced the activity of simple phenol derivatives, reaching, for the two Staphylococcus aureus strains in particular, the values obtained for their calixarenic parents. MTT viability assays were carried out to determine selectivity indexes.
Mourer
Maxime
M
SRSMC, UMR 7565 Nancy Université-CNRS, Groupe d'Etude des Vecteurs Supramoléculaires du Médicament, Faculté de Pharmacie, 5, rue Albert Lebrun, BP 80403, 54001 Nancy Cedex, France.
Dibama
Hugues Massimba
HM
Fontanay
Stéphane
S
Grare
Marion
M
Duval
Raphaël E
RE
Finance
Chantal
C
Regnouf-de-Vains
Jean-Bernard
JB
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000254:growth & development; D001550:Benzamidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008826:Microbial Sensitivity Tests; D019800:Phenol / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D001550:Benzamidines; D006146:Guanidines; C512158:tetra-para-guanidinoethyl-calix(4)arene; C005748:synthalin A; D019800:Phenol; C018961:hexamidine