TRIFLUOPERAZINE AND ITS METAL-COMPLEXES INHIBIT THE MOLONEY LEUKEMIA-VIRUS REVERSE-TRANSCRIPTASE

Reverse transcriptase plays an essential role in the early steps of th e replicative cycle of retroviruses. Because of the resistance against nucleoside analogue inhibitors such as 3'-azido-2:3'-dideoxythymidine , the importance of the investigation of non-nucleoside analogue inhib itors is increasing. We have investigated the influence of trifluopera zine (TFP - a species of phenothiazines) and its newly prepared TFP-me tal complexes (TFP-VO(IV), TFP-Cu(II), TFP-Ni(II), TFP-Pd(II), TFP-Sn( IV)). The compounds were tested on Moloney murine leukemia virus rever se transcriptase assay. The inhibitory effect of metal complexes was h igher than that of TFP. TFP-VO(IV) showed higher effectiveness compare d the added effect of parent tricyclic chemical and metal. Therefore w e concluded that the improved biological action depends on the formati on of metal complexes. This phenothiazine and its metal coordination c omplexes could become a new non-nucleoside analogue group of compounds inhibiting the retrovirus replication.