Cobalt mediated ring contraction reaction of lapachol and initial antibacterial evaluation of naphthoquinones derived from lapachol

Abstract

The synthesis of 2-hydroxy-2-(3-methylbut-2-enyl)-2H-indene-1,3-dione 3, from lapachol which involves a ring contraction via the Hooker intermediate 1,2-dihydroxy-2-(3-methylbut-2-en-1-yl)-3-oxo-2,3-dihydro-1H-indene-1-carboxylic acid 2 is described. Different pyranonaphthoquinone derivatives, obtained in our previous synthetic work, were screened for antimycobacterial (Mycobacterium tuberculosis) activity and against resistant strains of Gram-positive (Bacillus cereus and Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The results indicated significant activity of all the tested samples against M. tuberculosis and only moderate activity against the Gram-positive and Gram-negative bacteria.

Synthesis of New 2-N,N' ­ dialkylamino-1,4-naphthoquinone Derivatives: Concerning the Reactivity of Lapachol with Secondary Amines

“…Even if (1a) was partially hydrogenated at the side chain of 2-methoxylapachol yielding (7a) 19 no product was formed yet (Scheme 3). This last compound was used to probe if the basic amines could abstract the poorly acidic allylic hydrogen at C-1' in (1a) 20 thus explaining perhaps the formation of many byproducts in the observed reactions. However, a very similar behavior in TLC was observed from (1a) and (7a).…”

Cytotoxicity of lapachol metabolites produced by probiotics

“…The biological activities of lapachol and its derivatives have been widely studied since the 60's and include antibacterial activity against Mycobacterium tuberculosis and other micro‐organisms (Eyong et al . ), anti‐inflammatory (Landa et al . ), moluscicidal (Silva et al .…”

“…The biological activities of lapachol and its derivatives have been widely studied since the 60's and include antibacterial activity against Mycobacterium tuberculosis and other micro-organisms (Eyong et al 2012), anti-inflammatory (Landa et al 2013), moluscicidal (Silva et al 2005), antimalarial (Kapadia et al 2001), activity against Trypanossoma cruzi (Salas et al 2008), among others . Recently, the neurological activities of lapachol were studied and its antidepressant activity was shown (Eyong et al 2013a), as well as it was proved its potential gastroprotective effect (Theoduloz et al 2012).…”

Antifungal and Cytotoxic Assessment of Lapachol Derivatives Produced by Fungal Biotransformation

“…Although several bioactivities of lapachol (1) have already been demonstrated, there are few studies about its metabolites. Bai and co-workers recently pointed out nine phase I and four phase II metabolites after in vivo metabolism of 1.…”

“…Given the pharmacological potential of lapachol (1) and the desire to find new derivatives with enhanced activity, research of the microbial metabolism of this compound could be an alternative tool to produce new drugs. The general aim of this work was to show that the filamentous fungi Mucor circinelloides and Botrytis cinerea are able to modify the structure of lapachol (1) and that this is useful in assessing the effects of microbial metabolism on drug performance and toxicity. Avicequinone-A (2) was reported as a component of Avicennia alba [19,22].…”