Abstract:Vários estudos têm mostrado o potencial citotóxico de derivados da nor-β-lapachona contra células tumorais. Considerando a nor-β-lapachona um importante protótipo, uma série inédita de nor-β-lapachonas substituídas em C-3 foi sintetizada através de uma nova metodologia sintética envolvendo intermediário sintético 3-hidróxi-nor-β-lapachona para o acoplamento de alguns nucleófilos contendo núcleos derivados de carboidratos ou 2H-pirazóis. Todos os derivados foram avaliados frente a quatro linhagens de células tu… Show more
“…(synon. Tabebuia, Bignoniaceae family) [ 4 ] and first isolated from Tabebuia avellanedae, in 1882 by Paternó [ 5 ], was used as an antiplasmodial drug during World War II, when there was a shortage of quinine, the only available antimalarial agent at that time [ 6 ]. Since the pioneering work of Wendel (1946), who demonstrated that lapachol ( 2 , Figure 1 ) was active against P. vivax [ 7 ], numerous publications reported on the antiplasmodial activity of naphthoquinones leading to the development of atovaquone ( 3 , Figure 1 ), a totally synthetic hydroxy-1,4-naphthoquinone [ 4 ].…”
A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation.
“…(synon. Tabebuia, Bignoniaceae family) [ 4 ] and first isolated from Tabebuia avellanedae, in 1882 by Paternó [ 5 ], was used as an antiplasmodial drug during World War II, when there was a shortage of quinine, the only available antimalarial agent at that time [ 6 ]. Since the pioneering work of Wendel (1946), who demonstrated that lapachol ( 2 , Figure 1 ) was active against P. vivax [ 7 ], numerous publications reported on the antiplasmodial activity of naphthoquinones leading to the development of atovaquone ( 3 , Figure 1 ), a totally synthetic hydroxy-1,4-naphthoquinone [ 4 ].…”
A total of 28 lapachol-related naphthoquinones with four different scaffolds were synthesized and spectroscopically characterized. In vitro antiplasmodial activity was assayed against the chloroquine-resistant Plasmodium falciparum W2 strain by the parasite lactate dehydrogenase (pLDH) method. Cytotoxicity against Hep G2A16 cell was determined by the MTT assay. All compounds disclosed higher in vitro antiplasmodial activity than lapachol. Ortho- and para-naphthoquinones with a furan ring fused to the quinonoid moiety were more potent than 2-hydroxy-3-(1′-alkenyl)-1,4-naphthoquinones, while ortho-furanonaphthoquinones were more cytotoxic. Molecular docking to Plasmodium targets Pfcyt bc1 complex and PfDHOD enzyme showed that five out of the 28 naphthoquinones disclosed favorable binding energies. Furanonaphthoquinones endowed with an aryl moiety linked to the furan ring are highlighted as new in vitro antiplasmodial lead compounds and warrant further investigation.
“…This compound has been the basis for the synthesis of several important analogues or derivatives with improved biological activities [ 12 , 13 , 14 , 15 , 16 , 17 ]. Recently, it was demonstrated that the modification of the dihydrofuran ring of nor-β-lapachone ( 1 ) could considerably change its activity against cancer cells [ 18 , 19 , 20 , 21 ], Trypanosoma cruzi ( T. cruzi ) [ 22 , 23 , 24 , 25 , 26 ], and candidal agents [ 27 ]. Indeed, the triazolyl series of compounds 2 and the arylamine group of compounds 3 are very active against some cancer cell lines and T. cruzi , respectively ( Figure 1 ).…”
New sulfonyl-lapachones were efficiently obtained through the catalytic oxidation of arylthio- and cyclohexylthio-lapachone derivatives with hydrogen peroxide in the presence of a Mn(III) porphyrin complex. The antibacterial activities of the non-oxidized and oxidized lapachone derivatives against the Gram-negative bacteria Escherichia coli and the Gram-positive bacteria Staphylococcus aureus were evaluated after their incorporation into polyvinylpyrrolidone (PVP) micelles. The obtained results show that the PVP-formulations of the lapachones 4b–g and of the sulfonyl-lapachones 7e and 7g reduced the growth of S. aureus.
“…9 Lately, diverse lapachone derivatives have been reported as potent cytotoxic drugs against different cancer cell lines. 10 In this regard, advances in the synthesis of lapachones with potent antitumor activity have been accomplished via modification of the A-and C-rings, 11 with recent progress being achieved by da Silva Júnior, 12 Pinto, 13 Hong, 14 Ferreira, 15 Bonifazi,16 among others 17 (Scheme 1A).…”
Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.
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