Antiviral activities of gossypol and its derivatives against herpes simplex virus type II

doi:10.1016/0031-6989(86)90023-8

Pharmacological Research Communications

Volume 18, Issue 11, November 1986, Pages 1063-1073

https://doi.org/10.1016/0031-6989(86)90023-8 Get rights and content

Abstract

Gossypol, a disesquiterpene obtained from cottonseed oil, and a series of peri-acylated gossylic nitriles were compared for their antiviral activities against HSV-II and for their toxicities to the host Vero cells. All of the peri-acylated gossylic nitriles exhibited lower cytotoxicities to the host cell than did the parent compound gossypol. Both gossypol and the series of derivatives exhibited antiviral activities against HSV-II when the virus was treated with drug at concentrations as low as 5 × 10⁻⁷ $M$ . Two of the derivatives, gossylic nitrile-1, 1′-diacetate and gossylic nitrile-1, 1′-divalerate, were capable of inhibiting viral multiplication in Vero cells that were infected with virus before administration of the drug. The results of this study indicate that modification of the aldehyde functional groups on gossypol lowers the toxicity of this drug but does not abolish its antiviral properties. Derivatives of gossypol may be useful antiviral agents.

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Gossypol is a polyphenolic compound isolated from cottonseed. There are two optical enantiomers of gossypol, (−)-gossypol and (+)-gossypol. Gossypol exists as three different tautomers, aldehyde, ketone and lactol. Gossypol is toxic and provides a protective mechanism for cotton plants against pests. Gossypol was used as a male contraceptive in China in the 1970s. It was eventually abandoned due to noticeable side effects, disruption of potassium uptake and incomplete reversibility. Gossypol has gained considerable research interest due to its attractive biological activities, especially antitumor and antivirus. Gossypol derivatives are prepared by a structural modification to reduce toxicity and improve their therapeutic effect. This review depicts the bioactivity and regulation mechanisms of gossypol and its derivatives as drug lead compounds, with emphasis on its antitumor mechanism. The design and synthesis of pharmacologically active derivatives based on the structure of gossypol, such as gossypol Schiff bases, apogossypol, gossypolone, are thoroughly discussed. This review aims to serve as a reference for gossypol-based drug discovery and drug design.
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Citation Excerpt :
Previous studies have indicated that gossypol targets the enzyme reverse transcriptase (Lin et al., 1989; Polsky et al., 1989). However, it is worth noting that all previous reports of antiviral activity by gossypol and any derivatives thereof involved enveloped viruses (Dorsett et al., 1975; Lin et al., 1989; Radloff et al., 1986; Royer et al., 1991; Vichkanova et al., 1970; Wichmann et al., 1982). Although circumstantial, this fact suggests that gossypol and gossypol derivatives may interfere with interactions between the virus envelope and the plasma membrane of the host cell, thereby inhibiting the invasion process (Royer et al., 1991).
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Antiviral activities of gossypol and its derivatives against herpes simplex virus type II

Abstract

J. Pharm. Sci.

Toxicology

Env. Research

Contraception

FEBS Let.

Contraception

Am. J. Obstet. Gynecol.

Residue Reviews