Synthesis and preliminary pharmacological evaluation of new (+/-) 1,4-naphthoquinones structurally related to lapachol.

Abstract

Seven new 1,4-naphthoquinones structurally related to lapachol were synthesized from lawsone and oxygenated arylmercurials. These compounds can also be seen as pterocarpan derivatives where the A-ring was substituted by the 1,4-naphthoquinone nucleus. Pharmacological screening provided evidence of significant biological activities, including effects against proliferation of the MCF-7 human breast cancer cell line, against Herpes Simplex Virus type 2 infection, and against snake poison-induced myotoxicity. One derivative displaced flunitrazepam binding and showed benzodiazepine-like activity, suggesting novel neuroactive structural motifs.

• Authors: Alcides J M da Silva, Camilla D Buarque, Flávia V Brito, Laure Aurelian, Luciana F Macedo, Linda H Malkas, Robert J Hickey, Daniele V S Lopes, François Noël, Yugo L B Murakami, Noelson M V Silva, Paulo A Melo, Rodrigo R B Caruso, Newton G Castro, Paulo R R Costa
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 10 Issue 8 Pg. 2731-8 (Aug 2002) ISSN: 0968-0896 [Print] England
• PMID: 12057662 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Crotalid Venoms
• GABA-A Receptor Antagonists
• Naphthoquinones
• Neurotoxins
• lapachol

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Antiviral Agents (chemical synthesis, pharmacology)
• Cell Division (drug effects)
• Crotalid Venoms (antagonists & inhibitors)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• GABA-A Receptor Antagonists
• Herpesvirus 2, Human (drug effects)
• Humans
• Naphthoquinones (chemical synthesis, pharmacology)
• Neurotoxins (antagonists & inhibitors)
• Rats
• Structure-Activity Relationship
• Tumor Cells, Cultured