521-49-3

Upstream product

• 870-63-3 prenyl bromide 
• 83-72-7 2-hydroxynaphtho-1,4-quinone 
• 42164-69-2 Lawsone 2-isopentenyl ether 
• 64469-16-5 2-(1,1-dimethylprop-2-enyl)-3-hydroxy-naphthalene-1.4-dione 

Relevant academic research and scientific papers

NbCl5 mediated biomimetic cascade reaction: Efficient and scalable one-pot synthesis of dunnione and nor-β-lapachone

A regioselective biomimetic synthesis of bioactive natural products dunnione and nor-β-lapachone is described. This cascade provides a new strategy of a one-pot process mediated by Lewis acid NbCl5 involving a tandem Claisen rearrangement-cyclization reaction. This procedure was efficient, mild, and easily scalable that avoided using highly hazardous concd H2SO4.

Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.

Synthesis and evaluation of (±)-dunnione and its ortho-quinone analogues as substrates for NAD(P)H:quinone oxidoreductase 1 (NQO1)

Natural product (±)-dunnione (2) and its ortho-quinone analogues (3-8) were synthesized and found to be substrates for NQO1. The structure-activity relationship study revealed that the biological activity was favored by the presence of methyl group at the C ring and methoxy group at the A ring. The docking studies supported the rationalization of the metabolic studies. Deeper location in the active site of NQO1, interactions with hydrophobic pocket and C-H...π interactions with the adjacent Phe178 residue contributed to the better catalytic efficiency and specificity to NQO1. Cytotoxicity studies and determination of superoxide (O2-) production in the presence and absence of the NOQ1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling.

Synthesis, Characterization, and Antileukemic Properties of Naphthoquinone Derivatives of Lawsone

Naphthoquinones are considered privileged structures for anticancer drug molecules. The Heck reaction of 2-hydroxy-1,4-naphthoquinone (lawsone) with 1-bromo-3-methyl-2-butene offered easy access to lapachol. Several naturally occurring linear and angular heterocyclic quinoids (α-lapachone, β-lapachone, dunnione, and related analogues) were prepared from lapachol. Furthermore, we demonstrated that the synthetic naphthoquinones inhibit cell proliferation in human leukemia HL-60 cells. In particular, angular-type derivatives were found to possess moderate cytotoxicity and to elevate the levels of intracellular glutathione disulfide (GSSG). Our work highlights the significant potential of naturally occurring angular-series naphthoquinones as antileukemic agents.

PHARMACEUTICAL COMPOSITION FOR TREATMENT AND PREVENTION OF RESTENOSIS

Provided is a pharmaceutical composition for the treatment and/or prevention of restenosis including (a) a therapeutically effective amount of a particular compound represented by Formula 1 and 2, or a pharmaceutically acceptable salt, prodrug, solvate or isomer thereof, and (b) a pharmaceutically acceptable carrier, a diluent or an excipient, or any combination thereof.

PHARMACEUTICAL COMPOSITION FOR THE TREATMENT AND PREVENTION OF DISEASES INVOLVING IMPOTENCE

Disclosed is a pharmaceutical composition for the treatment and/or prevention of erectile dysfunction, comprising (a) a therapeutically effective amount of a compound represented by Formula 1 or 2, and (b) a pharmaceutically acceptable carrier, a diluent or an excipient, or any combination thereof.