Episome 性感染性伝達系に作用する物質に関する研究(第 1 報) : Acridine 誘導体の多剤耐性伝達阻止作用と化学構造との関係

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概要

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• 1) The inhibitory action of 17 compounds of acridine derivatives and its related compounds on the multiple-drug-resistance transfer from the resistant donor Shigella flexneri 3a strain MZ17R to the sensitive recipient E. coli strain K-12 C25S and the inverse transfer from the resistant donor E. coli strain K-12 C17R to the sensitive recipient Shigella flexneri 3a strain MZS were examined and the following results were obtained. Among the compounds tested, proflavine, acetylproflavine, acridine orange, acridine yellow, acriflavine and thioflavine T inhibited the multiple-drug-resistance transfer in a low concentration. The minimal concentration of each compound required for complete inhibition on the both transfer system (C17R⇾MZS and MZ17R⇾C25S) were respectively as follows : proflavine 5 and 20μg./ml., acetylproflavine 10 and 20μg./ml., acridine orange 40 and 80μg./ml., acridine yellow 10 and 40μg./ml., acriflavine 5 and 10μg./ml. and thioflavine T 10 and 80μg./ml. The minimal concentration required for the inhibition of the multiple-drug-resistance (factor) transfer from C17R to MZS was lower than that in the transfer from MZ17R to C25S. 2) A new evaluation method that excluded the antibacterial activity was devised. According to this method, acrinol was proved to have a superior antibacterial activity to the inhibitory one on the multiple-drug-resistance transfer. Hence, acrinol was considered not to have a specific inhibitory effect on the multiple-drug-resistance transfer from MZ17R to C25S but to affect slightly the transfer system from C25R to MZS. 3) From the observation of the chemical structures and the inhibitory activity of acridine derivatives on the multiple-drug-resistance transfer system, NH_2 or N (CH_3)_2 in position 3 and 6,CH_3 in position 2 and 7,and CH_3 or H and chlorine in position 10 of acridine nucleus were necessary for the activity. The acridine itself and its N-oxide, propionamido or benzamido in position 3 and 6 and ethoxy or methoxy radicals in position 2 or 7 of acridine nucleus such as N, N-dipropionylproflavine, N, N-dibenzoylproflavine, acrinol and acrinamine (atabrine) showed a reduced activity. Neutral red, thionine and methylene blue, in which carbon in position 9 of acridine was substituted with nitrogen or sulfur, thioflavine S, and acridine red presented also reduced activity. In the comparison of thioflavine T and thioflavine S, it might be of interest that the former had the inhibitory activity on the multiple-drug-resistance transfer system, but the latter did not.

• 共立薬科大学の論文
• 1965-05-20

著者

• 小川 芳子

  共立薬科大学基礎教育講座

• 菊地 和子

  共立薬大微生物学教室

• 岩崎 紀和子

  薬化学教室

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• Episome性感染性伝達系に作用する物質に関する研究 (第1報) : Acridine誘導体の多剤耐性伝達阻止作用と化学構造との関係

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