The antibacterial action of some stilbene derivatives.

Early types of antibacterial substances were not specifically antibacterial, but were usually toxic to all living cells, and were of value only in so far as they could be employed without serious damage to the host. The search for more suitable antibacterial agents resulted in the preparation and testing of many substances of widely different constitution, and it was from the empirical yet systematic investigations of one such class of chrysoidine dyestuff that knowledge of the activity of sulphanilamide arose. The growing evidence that the antibacterial action of sulphanilyl drugs was due to competition with an enzymic metabolic process suggested to Fildes [1940] a new approach to the problem. This was the design of antibacterial agents by the synthesis of compounds with a close spatial resemblance to substances vital to, or closely associated with, bacterial growth and reproduction. These growth substances include the water-soluble vitamins of the animal world, which now appear to be essential to the life of all growing cells. The method has been recently used in a sufficiently diverse series of independent investigations to confirm the principle [Mcflwain, 1943]. Other compounds which exert a pronounced physiological activity in minute concentration are the animal hormones related to cyclopentanophenanthrene; for example, oestradiol, when injected into an ovariectomized rat of 50 g. body weight in a dose of 02 jig., is capable of doubling the weight of the uterus; with a blood volume of 2 ml., this represents an activity at a concentration of 1 in 107. These compounds are not known to be hormones for the vegetable kingdom, but they are widely distributed in nature and are probably constituents of all growing cells, being found in all plants and bacteria [Aschheimn & Hohlweg, 1933], as well as in all animals. It seems to us that these compounds can readily be incorporated into the living cell, and that such molecules constitute suitable material which, while not necessarily competitive with known essential systems, is capable of modification to contain known antibacterial groupings. Synthetic work in the cyclopentanophenanthrene series is difficult, and it is fortunate that the work of Dodds, Golberg, Lawson & Robinson [1939] provided, in the diethylstilboestrols, simple substances with space configurations similar to those of the. naturally occurring compounds, and with their intense physiological activity. We have prepared and tested a number of compounds in this series for antibacterial properties and have found some of them very powerfully bactericidal. As with the oestrogenic properties of compounds in, this series, the antibacterial activities vary considerably with the structure ofthe molecule, though these variations are not altogether analogous. The compounds tested are set out in Table 1 and fall into seven main classes: