Synthesis and preliminary pharmacological evaluation of new (+/-) 1,4-naphthoquinones structurally related to lapachol.
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.
da Silva
Alcides J M
AJ
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.
Buarque
Camilla D
CD
Brito
Flávia V
FV
Aurelian
Laure
L
Macedo
Luciana F
LF
Malkas
Linda H
LH
Hickey
Robert J
RJ
Lopes
Daniele V S
DV
Noël
François
F
Murakami
Yugo L B
YL
Silva
Noelson M V
NM
Melo
Paulo A
PA
Caruso
Rodrigo R B
RR
Castro
Newton G
NG
Costa
Paulo R R
PR
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
D000970:Antineoplastic Agents; D000998:Antiviral Agents; D003435:Crotalid Venoms; D058787:GABA-A Receptor Antagonists; D009285:Naphthoquinones; D009498:Neurotoxins; C008252:lapachol