Antiherpes virus activities of new 6-19 carbon-bridged steroids and some synthetic precursors.
Three synthetic 6,19-carbon bridged steroids: 3beta,20beta-diacetyloxy-5alpha-chloro-19a(R)-hydroxy-6,19-methanopregnane, 3beta,20beta-diacetyloxy-5alpha-chloro-6,19-methanopregnane, 6,19-methanopregn-4-ene-3,20-dione and four synthetic precursors: 3beta,20beta-diacetyloxy-19-hydroxypregn-5-ene, 3beta,20beta-diacetyloxy-pregn-5-en-19-al, 3beta,20beta-diacetyloxy-19(E)-(methoxymethylidene)-pregn-5-ene and 20beta-acetyloxy-3beta-hydroxy-19(E)-(methoxymethylidene)-pregn-5-ene were tested against herpes virus replication in cell cultures. Several compounds were cytotoxic for stationary cells. Antiviral studies performed with all compounds against HSV-1 indicated a dose-dependent virus susceptibility with selectivity indexes (SI) values in the range 1.7-183.2. Selected compounds were also tested against HSV-2 and the SI values obtained were in the range of 31-273. Attempts to reveal the step of virus multiplication affected by pregnanes were performed with one compound. HSV-1 virus incubation with the compound did not alter the ability of virus particles to infect cells; moreover, neither virus adsorption nor penetration appeared to be affected. The drug must be present during at least the first 7 h of the virus cycle to inhibit more than 90% of virus production. All these results suggest that these novel molecules interfere with an intracellular step of virus multiplication, thus behaving like true antivirals.
Petrera
Erina
E
Laboratory of Virology, Department of Biological Chemistry, School of Science, University of Buenos Aires, Buenos Aires, Argentina.
Joselevich
Maria
M
Ghini
Alberto
A
Burton
Gerardo
G
Coto
Celia E
CE
D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006564:Herpesviridae / Q000187:drug effects*; D006566:Herpesviridae Infections / Q000188:drug therapy / Q000821:virology; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D011278:Pregnanes / Q000138:chemical synthesis / Q000494:pharmacology; D013256:Steroids / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014709:Vero Cells; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D011278:Pregnanes; D013256:Steroids