Antiherpes Virus Activities of New 6–19 Carbon-Bridged Steroids and Some Synthetic Precursors

• Published in: Antiviral chemistry & chemotherapy 2003-10, Vol.14 (5), p.243-248
• Main Authors: Petrera, Erina, Joselevich, Maria, Ghini, Alberto, Burton, Gerardo, Coto, Celia E
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - chemical synthesis; Antiviral Agents - pharmacology; Biological and medical sciences; Cercopithecus aethiops; Cytotoxicity; Dose-Response Relationship, Drug; Herpes viruses; Herpesviridae - drug effects; Herpesviridae Infections - drug therapy; Herpesviridae Infections - virology; Herpesvirus; Herpesvirus 1, Human - drug effects; Herpesvirus 2, Human - drug effects; Humans; Medical sciences; Pharmacology. Drug treatments; Pregnanes - chemical synthesis; Pregnanes - pharmacology; Steroid hormones; Steroids; Steroids - chemical synthesis; Steroids - pharmacology; Structure-Activity Relationship; Vero Cells; Virus Replication - drug effects
• ISSN: 2040-2066; 0956-3202; 2040-2066
• DOI: 10.1177/095632020301400503

Three synthetic 6,19-carbon bridged steroids: 3β,20β-diacetyloxy-5α-chloro-19a(R)-hydroxy-6,19-methanopregnane, 3β,20β-diacetyloxy-5α-chloro-6,19-methanopregnane, 6,19-methanopregn-4-ene-3,20-dione and four synthetic precursors: 3β,20β-diacetyloxy-19-hydroxypregn-5-ene, 3β,20β-diacetyloxy-pregn-5-en-19-al, 3β,20β-diacetyloxy-19(E)-(methoxymethylidene)-pregn-5-ene and 20β-acetyloxy-3β-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.