A new approach for the synthesis of 3-substituted cytotoxic nor-β-lapachones

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 tumorais. Duas das substâncias apresentaram moderada citotoxicidade, enquanto as demais inibiram fortemente todas as linhagens tumorais testadas.Several studies have demonstrated the cytotoxic potential of nor-β-lapachone derivative against cancer cells. Considering nor-β-lapachone as an important prototype, a set of new 3-substituted nor-β-lapachones was synthesized by a new synthetic route that involves the use of synthetic intermediate generated for coupling with several nucleophiles containing the carbohydrate and 2H-pyrazole substituent moieties. All the compounds were screened against four tumor cell lines. Two of the compounds showed moderate cytotoxicity, while the other compounds strongly inhibit all tested cancer cell lines.

Synthesis, SAR, and Docking Studies Disclose 2-Arylfuran-1,4-naphthoquinones as In Vitro Antiplasmodial Hits

“…(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 ].…”

Efficient Catalytic Oxidation of 3-Arylthio- and 3-Cyclohexylthio-lapachone Derivatives to New Sulfonyl Derivatives and Evaluation of Their Antibacterial Activities

“…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 ).…”

On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

“…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).…”