Synthesis and Antimicrobial Activity of Phenazine Derivatives (Ⅱ)

페나진 유도체의 합성과 항균성에 관한 연구 (제 2 보)

8-Acyl-2-hydroxyphenazine-5,10-dioxides and 8-acyl-2-aminophenazine-5,10-dioxides were synthesized by the reaction of hydroquinone and 4-aminophenol with 6-acylbenzofuroxans which had been obtained from acetanilide and n-acyl chlorides bearing butanoyl, hexanoyl and octanoyl groups. The antimicrobial activities of these phenazine dioxide derivatives were investigated in terms of minimum inhibitory concentration by the common twofold dilution technique. It was observed that the antimicrobial activity of the phenazine dioxide derivatives bearing octanoyl group was stronger than that of those bearing butanoyl and hexanoyl groups in gram positive microorgamisms, but it was observed that the antimicrobial activity and the number of the carbon atom of acyl groups did not have any relation in gram negative microorganisms. When the activity of xanthine oxidase which is the key enzyme in the generation of superoxide anion radical ($O_2^-$), was measured in the presence of phenazine dioxide derivatives, the inhibitory action of the enzyme activity of 8-acyl-2-hydroxyphenazine-5,10-dioxides was increased in accordance with the number of the carbon atom of acyl groups.

아세트아닐리드와 부타노일, 헥사노일, 옥타노일기를 가진 n-acyl chloride류로부터 6-acylbenzofuroxan류를 합성하고, 이들과 히드로퀴논 및 4-아미노페놀을 반응시켜 8-Acyl-2-hydroxyphenazine-5,10-dioxide류와 8-acyl-2-aminophenazine-5,10-dioxide류를 합성하였다. 이들 phenazine dioxide 유도체의 향균성을 희석법에 의하여 최소 발육저지 농도로서 조사하였는데, 그람양성균에서 옥타노일기를 가진 phenazine dioxide 유도체들이 부타노일기나 헥사노일기를 가진 유도체를 보다 항균성이 더 강하였으나, 그람음성균에서는 항균성과 아실기의 탄소수와는 관계가 없다는 것은 알았다. 활성산소($O_2^-$) 생성의 주효소인 xanthine oxidase의 활성을 phenazine dioxide류의 효소활성 저해작용은 아실기의 탄소수가 증가함에 따라 증가하였다.