Abstract
Thirty-three Mannich bases of 2,2'-methylene bis (3,4, 6-trichlorophenoxy-acetic acid) were synthesized hexachlorophene as potential antimicrobial agents and tested against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Trichophyton rubrum, Microsporum gypseum, Epidermophyton floccosum, Aspergillus niger and Aspergillus oryzae in vitro. It was found that: 1) 2,2'-Methylene bis [${\alpha}$-(3, 4, 6-trichlorophenoxy)-${\beta}$- (N,N -diethylamino) propionic acid] and 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(N, N-dimethynlamo) propionoic acid] were active against Staphylococcus aureus and Bacillus subtilis at the concn. of 1 $\mu\textrm{g}$/$m\ell$ respectively; 2) 2,2'-Methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(m-hydroxy-p-carboxyphenylamino) propionic acid] and 2,2'-methylene bis [${\alpha}$-(3, 4, 6-trichlorophenoxy)-${\beta}$-(cyclohexylamino) propionic acid] were active against Trichophyton-rubrum at the concn. of 2 $\mu\textrm{g}$/$m\ell$ respectively; 3) 2,2'-Methylene bis [${\alpha}$-3,4,6-trichlorophenoxy)-${\beta}$-(m-hydroxy-p-carboxyphenyl-amino) propionic acid] and 2,2'-methylene bis [${\alpha}$-(3,4,6-trcihlorophenoxy)-${\beta}$-(piperidino) propionic acid] were active against Microsporum gypseum at the concn. of 2 $\mu\textrm{g}$/$m\ell$ respectively; 4) 2,2'-Methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(m-hydroxyphenylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3, 4,6-trichlorophenoxy)-${\beta}$-(m-hydroxy-p-carboxy phenylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(o-chlorophenylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(o-chloro-p-nitrophenylamino) propionic acid], 2,2'-methylene bis [${\alpha}$- (3,4,6-trichlorophenoxy)-${\beta}$-(methylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(hydroxylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(cyclohexylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorphenoxy)-${\beta}$-(morpholino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(p-sulfophenylamino) propionic acid] and 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(4-sulfu-l-nayphthlamino) aoi!c rppioncd (were active against Epidermophyton floccosum at the concn. of 1 $\mu\textrm{g}$/$m\ell$ respectively; 5) 2,2'-Methlene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(m-hydroxyphenylamino) propionic acid], 2,2'-methylene bis (a-(3,4,6-trichlorophenoxy)-${\beta}$-(m-hydroxy-p-carboxyphenylamino) propionic acid], 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(p-methylphenylamino) propionic acid] and 2,2'-methylene bis [${\alpha}$-(3,4,6-trichlorophenoxy)-${\beta}$-(hydroxylamino) propionic acid] were active against Aspergillus niger and Aspergillus oryzae at the concn. of 1 $\mu\textrm{g}$/$m\ell$ respectively.
34종의 Hexachlorophene유도체가 합성되었으며 그 각각의 화합물에 대하여 항균성시험이 행해졌다. 검정균은 세종류의 세균과 무좀균(백성균)을 포함한 5종류의 진균류이다. 시험결과는 1. 2,2'-Methylene bis [$\alpha$-(3,4,6-trichlorophenoxy)-$\beta$-(N,N-diethylamino) propionic acid] 및 2,2'-methylene bis [$\alpha$-3,4,6-trichlorophenoxy)-$\beta$-(N,N-dimethylamino) propionic acid] 는 Sta. aureus와 B.subtilis에 대해 강한 항균작용을 나타냈다. 2. 2,2'-methylene bis [$\alpha$-(3,4,6-trichlorophenoxy)-$\beta$-(m-hydroxy-p-carbozyphenylarnino ) propionic acid]는 특히 진균류의 생장저해작용이 강하며 Trichophyton rubrum 및 Microsporum gypseum에는 2 $\mu\textrm{g}$/$m\ell$의 농도에서 항균성을 가지며, Epidermophyton floccosum Aspergillus niger 및 Aspergillus oryzae에 대해서는 1 $\mu\textrm{g}$/$m\ell$의 농도에서 항균성을 나타냄으로서 Hexachlorophene 항균성의 10배 내지 50배의 항균력을 가진다. 3. 34종류의 합성물질중 원 Hexachlorophene에 비해 5종류의 진균류에 대해 부분적으로나마 강한 항균력을 나타내는 물질은 23종류였고 3종류의 세균에 대해선 13종류였다.