14918-66-2Relevant articles and documents
Design and Application of a High-Throughput, High-Content Screening System for Natural Product Inhibitors of the Human Parasite Trichomonas vaginalis
King, Jarrod B.,Carter, Adam C.,Dai, Wentao,Lee, Jin Woo,Kil, Yun-Seo,Du, Lin,Helff, Sara K.,Cai, Shengxin,Huddle, Brandt C.,Cichewicz, Robert H.
, p. 1456 - 1470 (2019)
It is estimated that Trichomonas vaginalis affects an astonishing 3.9% of the world's population, and while many of those infected are asymptomatic, progression of the disease can lead to serious health problems. Currently, the nitroimidazoles constitute the only drug class approved to treat trichomoniasis in the United States, which makes the spread of drug resistance a realistic concern. We developed a new image-based, high-throughput, and high-content assay for testing natural products (purified compounds and extracts) for antitrichomonal activity. Applying this assay system to a library of fungal natural product extracts led to the identification of three general classes of natural product inhibitors that exhibited moderate to strong activities against T. vaginalis: anthraquinones, xanthone-anthraquinone heterodimers, and decalin-linked tetramic-acid-containing metabolites. The tetramate natural products emerged as the most promising candidate molecules with pyrrolocin A (51) exhibiting potent activity against the parasite (EC50 = 60 nM), yet this metabolite showed limited toxicity to mammalian cell lines (selectivity index values of 100 and 167 versus 3T3 fibroblast and Ect1 normal cervical cells, respectively). The imaging-based assay system is a powerful tool for the bioassay-guided purification of single-component antitrichomonal biomolecules from complex natural product mixtures.
Direct amination of naphthazarin, juglone, and some derivatives
Arnone, Alberto,Merlini, Lucio,Nasini, Gianluca,De Pava, Orso Vajna
, p. 2569 - 2577 (2007)
Mono- and diamino-derivatives of naphthazarin, 2-methoxynaphthazarin, juglone and their methylethers were prepared by reaction with ammonia. The structure of the products was established by NMR studies. Some compounds were tested for cytotoxic activity. C
Trimethyl orthoacetate as a convenient reagent for selective methylation of β-OH groups of (poly)hydroxynaphthazarins
Balaneva,Shestak,Novikov
, p. 55 - 63 (2019/04/25)
Trimethyl orthoacetate was found to be a convenient reagent for methylation of the β-OH groups of (poly)hydroxynaphthazarins. The substrates bearing one β-OH group react with MeC(OMe)3 to give the corresponding methoxy derivatives in 79–89% yields. Depending on the reaction conditions, methylation of substrates with two β-OH groups on the different and the same rings affords either the corresponding mono-O-methylated (43–70%) or di-Omethylated (71–78%) derivatives. Trimethyl orthoacetate offers a good alternative to CH2N2 in the preparative synthesis of O-methylated (poly)hydroxynaphthazarin derivatives.
Ru(II)-Catalyzed Site-Selective Hydroxylation of Flavone and Chromone Derivatives: The Importance of the 5-Hydroxyl Motif for the Inhibition of Aurora Kinases
Kim, Kiho,Choe, Hyeonjeong,Jeong, Yujeong,Lee, Jun Hee,Hong, Sungwoo
supporting information, p. 2550 - 2553 (2015/05/27)
An efficient protocol for Ru(II)-catalyzed direct C-H oxygenation of a broad range of flavone and chromone substrates was developed. This convenient and powerful synthetic tool allows for the rapid installation of the hydroxyl group into the flavone, chromone, and other related scaffolds and opens the way for analog synthesis of highly potent Aurora kinase inhibitors. The molecular docking simulations indicate that the formation of bidentate H-bonding patterns in the hinge regions between the 5-hydroxyflavonoids and Ala213 was the significant binding force, which is consistent with experimental and computational findings.