title: 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.affiliation: Laboratório de Química Bioorgânica (LQB), Núcleo de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Bloco H, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
authors.forename: Alcides J M
authors.initials: AJ
authors.lastname: da Silva
authors.forename: Camilla D
authors.initials: CD
authors.lastname: Buarque
authors.forename: Flávia V
authors.initials: FV
authors.lastname: Brito
authors.forename: Laure
authors.initials: L
authors.lastname: Aurelian
authors.forename: Luciana F
authors.initials: LF
authors.lastname: Macedo
authors.forename: Linda H
authors.initials: LH
authors.lastname: Malkas
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Hickey
authors.forename: Daniele V S
authors.initials: DV
authors.lastname: Lopes
authors.forename: François
authors.initials: F
authors.lastname: Noël
authors.forename: Yugo L B
authors.initials: YL
authors.lastname: Murakami
authors.forename: Noelson M V
authors.initials: NM
authors.lastname: Silva
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Melo
authors.forename: Rodrigo R B
authors.initials: RR
authors.lastname: Caruso
authors.forename: Newton G
authors.initials: NG
authors.lastname: Castro
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003435:Crotalid Venoms / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D058787:GABA-A Receptor Antagonists; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D009285:Naphthoquinones / Q000138:chemical synthesis* / Q000494:pharmacology; D009498:Neurotoxins / Q000037:antagonists & inhibitors; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003435:Crotalid Venoms; D058787:GABA-A Receptor Antagonists; D009285:Naphthoquinones; D009498:Neurotoxins; C008252:lapachol