ANTIVIRAL ACTIVITY OF ACRIDINYLAMINOALCOHOLS AND ACRIDINYLAMINOACID ESTERS

Abstract

Previously we have synthesized and characterized a series of acridinylaminoalcohols (Ia – Id) [1] and acridinylaminoacid esters (IIa – IId) [2], among which there are substances possessing antiviral properties with respect to the Rift Valley fever virus (RVFV). In order to check the validity of a hypothesis concerning the polymodal character of the antiviral action of such compounds [3, 4], it was of interest to determine their activity on the models of various viral infections, including DNA-containing strains. In this context, we have studied the activity of some of the previously synthesized compounds in a Vero cell culture with respect to herpes simplex virus (HSV). The reference drugs were camedone (carboximethylacridone sodium salt, III) [5] and amyxin (IV) [6]. It was established that the maximum activity is inherent in compounds Ia – Id, of which the most pronounced anti-HSV effect was observed for compounds Ia and Id (see Table 1). Compound IIa – IId and the reference drugs III and IV proved to be inactive with respect to the model employed. A comparison of these data with the results obtained in the tests on mice under the conditions of urgent prophylaxis of RVFV infection showed that the antiviral activity of compounds Ia – Id with respect to HSV cell culture varies generally in phase with the activity in animals. It is interesting to note the inversion of the relative activity of compounds Ic and Id (enantiomers) on passage from the in vivo to the in vitro model. The D-isomer Id is more active than the L-isomer Ic on the HSV cell model, but the latter exhibits a more pronounced protective effect in mice. Thus, aminoacridine derivatives are of interest from the standpoint of searching for new antiviral preparations.