59586-28-6Relevant academic research and scientific papers
Structural optimization of natural product nordihydroguaretic acid to discover novel analogues as AcrB inhibitors
Alenzy, Rawaf,Liu, Xingbang,Ma, Shutao,Ma, Yingang,Mowla, Rumana,Polyak, Steven W.,Song, Di,Teng, Yuetai,Venter, Henrietta,Wang, Yinhu
, (2019/12/24)
Drug efflux pumps confer multidrug resistance to dangerous bacterial pathogens which makes these proteins promising drug targets. Herein, we present initial chemical optimization and structure-activity relationship (SAR) data around a previously described efflux pump inhibitor, nordihydroguaretic acid (NDGA). Four series of novel NDGA analogues that target Escherichia coli AcrB were designed, synthesized and evaluated for their ability to potentiate the activity of antibiotics, to inhibit AcrB-mediated substrate efflux and reduce off-target activity. Nine novel structures were identified that increased the efficacy of a panel of antibiotics, inhibited drug efflux and reduced permeabilization of the bacterial outer and inner membranes. Among them, WA7, WB11 and WD6 possessing broad-spectrum antimicrobial sensitization activity were identified as NDGA analogues with favorable properties as potential AcrB inhibitors, demonstrating moderate improvement in potency as compared to NDGA. In particular, WD6 was the most broadly active analogue improving the activity of all four classes of antibacterials tested.
Preparation of tetrahydrodibenzocyclooctene lignans and spirodienones by hypervalent iodine oxidation of phenolic dibenzylbutyrolactones
Ward, Robert S.,Pelter, Andrew,Abd-El-Ghani, Atef
, p. 1303 - 1336 (2007/10/03)
Treatment of the dibenzylbutyrolactone 18 with PhI(OCOCF3)2 in trifluoroethanol gives as the major product either the spirodienone 28 or the tetrahydrodibenzocyclooctene 29, depending upon the length of time allowed for the reaction. Reaction of a second dibenzylbutyrolactone 19 under the same conditions gives the products 33, 34, 36 and 38, while 20 gives 43 directly. These reactions provide the first syntheses of spirodienones such as 28 and 33, which have been postulated as intermediates in the biosynthesis of tetrahydrodibenzocyclooctene lignans.
