Relationships between antiseptic action and chemical constitution with special reference to compounds of the pyridine, quinoline, acridine and phenazine series

Abstract

In the course of investigations on the antiseptic properties of certain basic benzene derivatives, it was shown that the methochloride of diaminoacridine was very highly antiseptic, and that, unlike other powerful antiseptics then known, its antibacterial activity was not reduced by the presence of blood serum (Browning, Gilmour, Gulbransen, Kennaway and Thornton, 2, 7). Diaminoacridine methochloride had been prepared by Benda (1) for Ehrlich, and was named by them trypaflavin on account of its powerful therapeutic properties in experimental trypanosome infections. We are not aware that its action on bacteria had been investigated prior to the work recorded in the above paper (2), although Shiga (10) published almost simultaneously results of his investigations on its action on V. choleræ The hydrochloride and sulphate of diaminoacridine were then found to be practically equal to the methochloride in antiseptic properties and in efficacy of action in serum (8). In the case of these aminoacridine substances the power of killing bacteria is exerted slowly; thus, with the methochloride acting on B. coli in serum, the concentration which proves lethal in 2 hours (1:20000) is five to ten times greater than that required to produce sterility after 24 hours; on the other hand, mercuric chloride and carbolic acid produce their maximum effect within 2 hours, whether they be tested in a solution containing a minute amount of protein (0·7 per cent, of Witte’s peptone) or in a rich protein medium such as serum. The acridine compounds, therefore, may be said to act especially as bacteriostatic agents (7, 8). This property, coupled with their relative innocuousness for mammalian tissues, as tested by toxicity for the living animal as a whole (4, 7), effect on phagocytosis (3, 7), and slight irritating action on the conjunctiva (7), suggested that these substances should be specially applicable for the purpose of restraining bacterial infections in the tissues. Thus the methochloride, under the name of acriflavine, and the sulphate of diaminoacridine base, as proflavine, found extensive use in the treatment of infected wounds during the late war, and also in the treatment of such relatively accessible infections as gonorrhoea. The present work records the investigations which have been made with lire view of tracing the source of the antiseptic property of diaminoacridine compounds by examining substances which may be regarded as fragments of the acridine molecule. The parent substance of the acridine derivatives is a compound of the following formula that is, a combination of two benzene and a pyridine ring. If the two side wings are removed, a pyridine nucleus remains; if only one wing is detached, a quinoline nucleus results. It seemed, therefore, possible that the antiseptic activity of acriflavine (diamino acridine methochloride) might reside either in the pyridine or quinoline nucleus, reinforced by one or more amino groups. It is for this reason that substances of this type were first examined. In addition, a series of acridine derivatives have been prepared and tested for their antiseptic power in order to determine, if possible, whether any law could be established relating chemical structure and antiseptic action within the group. Also, observations have been made upon phenazine compounds, on account of their close chemical relationship to the acridine group.

The HIF-1 antagonist acriflavine: visualization in retina and suppression of ocular neovascularization

“…Acriflavine has been known to have trypanocidal and anti-bacterial activity for nearly a century [40]. Its first clinical use was for treatment of gonorrhea, for which 40–80 mg was given intravenously at 2–3 day intervals [41].…”

Beyond DNA binding - a review of the potential mechanisms mediating quinacrine's therapeutic activities in parasitic infections, inflammation, and cancers

“…Originally developed as pigments and dyes, the pharmalogical properties of acridine compounds were first investigated by Ehrlich and Benda in 1912, as antiprotozoal agents that act upon trypanosome parasites and developed further by Carl Browning as antibacterial agents [1-3]. The use of acridines as antibacterial agents fell out of favor in the 1940's after the discovery and wide spread availability of penicillin to combat bacterial infections.…”

ChemInform Abstract: DEACTIVATION BEHAVIOR OF ARENES AND HETEROARENES. XVII. FLUORESCENCE QUENCHING OF CATIONS BY ANIONS

“…Abb. 2; c , bei langen Fluoreszenzlebensdauern kann das molnre Diffusioiisvolumen vernachlbssigt und die Stern-Volmer-Gleichung (8) Bei der nntersuchten Loschung von Kationen durch Anionen ist es notwendig, die C'oulo~~~bwechselwirkiing zu beriicksichtigen (10) (13) und /J = 0 (14) berechnet.…”