ACS Meeting News NATURAL PRODUCTS
Licorice compounds can inhibit drug-metabolizing enzymes Botanical supplements used to treat menopausal symptoms can interact with many biological targets down of pharmaceuticals in the body. Women seeking relief from menopausal Drugs or other molecules people insymptoms sometimes reach for botanical gest can alter the activity of certain CYP dietary supplements. Extracts from licenzymes and disrupt drug metabolism. orice, hops, and red clover contain phyInhibiting an enzyme that chews up a toestrogens that help mitigate hot flashes, certain drug can lead for example. HO CH3O OH to buildup of that medThese extracts also ication, potentially to contain a “mush” of toxic levels. Enhancing other compounds that enzyme activity, on the act on a multitude of O other hand, will accelerbiological targets with Licochalcone A ate clearance of the drug possible unintended from the body, rendering the medication consequences, according to Judy Bolton, less effective. head of the medicinal chemistry and pharStudying these kinds of drug-drug intermacognosy department at the University actions is required by the U.S. Food & Drug of Illinois, Chicago (UIC). Administration in pharmaceutical developBolton organized a session last week at ment, but no such requirements exist for the ACS national meeting in Washington, botanical supplement development. RichD.C., to discuss research elucidating the ard B. van Breemen, a colleague of Bolton’s biological effects of botanical suppleat UIC and director of the NIH-funded ments. In one talk, researchers reported Center for Botanical Dietary Supplements that licorice extracts can interfere with Research, works to fill in that knowledge drug-metabolizing enzymes. gap. His team at the center identifies potenThis suite of cytochrome P450 (CYP) tially harmful botanical-drug interactions. enzymes in the liver degrades potentially During a Division of Chemical Toxicoltoxic molecules, including by-products of ogy session at the ACS meeting, van Breenormal metabolism. The enzymes also are men discussed a recent study of extracts responsible for two-thirds of the break-
from three licorice plant species. His team looked for possible interactions between CYP enzymes and the extracts themselves, as well as 14 compounds isolated from the extracts. The team found that many of the extracts and compounds inhibited various CYP enzymes and that one licorice species in particular, Glycyrrhiza inflata, was extremely potent because of a compound called licochalcone A (Eur. J. Pharm. Sci. 2017, DOI: 10.1016/j.ejps.2017.07.034). Licochalcone A irreversibly inhibits the CYP3A4 enzyme, a critical component of the CYP family. Van Breemen’s team has three Phase II clinical studies approved, two of which are already under way, to study how licorice, hops, and red clover extracts interfere with drug metabolism in menopausal women. Mary F. Paine, an associate professor of pharmaceutical sciences at Washington State University, said interaction studies such as this one are “very valuable.” The ultimate goal, according to Paine, is to share definitive knowledge with consumers and health care providers about potential adverse botanical-drug interactions.—EMMA HIOLSKI
CHEMICAL BONDING
C RE D IT: S H UT T ERSTO C K
Triplet diradical cyclobutadiene spotted Carbon and silicon share many chemical properties, yet their low-coordinate compounds behave quite differently: For example, although C=C bonds are ubiquitous, Si=C and Si=Si bonds are rare, and the latter can be isolated only when sterically protected by large substituents. Those bonding differences stem from parameters including differences in electronegativity and the size of bonding orbitals, according to Yitzhak Apeloig of Technion—Israel Institute of Technology. During a lecture last week at the ACS national meeting in Washington, D.C., Apeloig described how he and his colleagues used that knowledge to observe an elusive diradical. Apeloig spoke in a symposium on theoretical modeling of
chemical bonding hosted by the Division of Physical Chemistry to honor Nobel Laureate Roald Hoffmann of Cornell University. (CH3)3Si Apeloig explained how double-bonded carbon and silicon anions and radicals (CH3)3Si have different structures and properties, and that silicon radicals are thermodynamically more stable than carbon radicals. By understanding that stability, Apeloig, working with Technion’s Boris Tumanskii, the University of Tsukuba’s Akira Sekiguchi, and others, used a combination of electron paramagnetic resonance spectroscopy (EPR) and computational work in 2015 to observe the first triplet diradical—a radical in which the two
unpaired electron spins are aligned in parallel—in a Si=Si compound. That work enabled the same team to now report the first specSi(CH3)3 troscopic observation of a triplet diradical electronic state of a heated cyclobutaSi(CH3)3 diene (shown), albeit one stabilized by trimethylsilyl groups (Angew. Chem. Int. Ed. 2017, DOI: 10.1002/anie.201705228). Cyclobutadiene is a classic model compound used to study antiaromaticity, but the triplet diradical of cyclobutadiene had not been observed because of its low stability. Studying the elusive species could aid organic synthesis and help design new electronic materials, Sekiguchi told C&EN.—STEVE RITTER AUGUST 28, 2017 | CEN.ACS.ORG | C&EN
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