NEWS OF THE WEEK
MEDICINAL CHEMISTRY: Lipophilic
compound kills more cancer cells
N
EW LIPOPHILIC bisphosphonate compounds
that act on multiple enzymes could lead to improved anticancer drugs as well as treatments for tropical diseases. Although bisphosphonate drugs were originally developed for osteoporosis and other bone diseases, recent clinical trials have demonstrated that they also have anticancer activity and immune-enhancing benefits. But current bisphosphonates may not be optimal against soft-tissue tumors because they bind strongly to bone. Now, an international team of 24 researchers led by chemistry professor Eric Oldfield of the University of Illinois, Urbana-Champaign, reports a lipophilic bisphosphonate called BPH-715 that is up to 200 times better at killing tumor cells and more bioavailable to soft-tissue tumors than traditional bisphosphonates (J. Amer. Chem. Soc., DOI: 10.1021/ja808285e). “Our compounds are tagged with a lipophilic tail so they bind less strongly to bone and more readily cross cell membranes,” making them more effective than current
PRIESTLEY HOUSE MAY BE SHUTTERED SCIENCE HISTORY: Pennsylvania State
budget cuts could halt operation of ACS Historic Chemical Landmark
S
TATE BUDGET CUTS may force closure of the
Joseph Priestley House, an ACS Historic Chemical Landmark in Northumberland, Pa., as early as this summer. An internal review by the Pennsylvania Historical & Museum Commission (PHMC), the state agency that runs the site, has recommended it be shuttered due to low visitation and limited potential for growth. Priestley is widely known for his 1774 discovery of oxygen in England. There are no other existing historical sites associated with Priestley. Five other historical sites in Pennsylvania were recommended for closure by the PHMC internal review because of budget cuts expected in the coming fiscal year. “When we say ‘close,’ in each case we are trying to find other solutions for the site,” PHMC Executive Director Barbara Franco says. “We are asking ourselves, ‘Who cares about this site? Who will help us solve this problem?’ ” She says PHMC will hold a public meeting
bisphosphonates at killing soft-tissue tumors in mice, Oldfield says. These new compounds also kick-start the production of 100 times more cancer-killing immune system T cells than current bisphosphonates, he adds. “Such lipophilic bisphosphonates may be suitable lead structures, or ideally preclinical candidates, in the search for novel anticancer agents,” says Wolfgang Jahnke, who studies bisphosphonate biology and chemistry at the Novartis Institutes of Biomedical Research, in Basel, Switzerland. Novartis makes zoledronate, a traditional bisphosphonate drug for treating excessive bone resorption. O Bisphosphonates in clinical use target an 9 enzyme called farnesyl diphosphate synthase (FPPS). Inhibiting it impairs cancer-cell-survival signaling pathways that involve synthesizing isoprenoids. Oldfield and coworkers engineered the lipophilic compounds to inhibit both FPPS and a similar enzyme called geranylgeranyl diphosphate synthase (GGPPS), which recent work has indicated may also be a viable target for anticancer drugs. Crystallographic studies demonstrate that BPH-715 binds FPPS but primarily inhibits GGPPS. Roberto Docampo, a biochemist at the University of Georgia, praises the “elegant structural and chemical studies.” He adds that lipophilic bisphosphonates may also be useful in developing drugs to treat African sleeping sickness and malaria, both of which have cellsignaling pathways that involve FPPS and GGPPS.—
O + N HO
P
OH P OH OH O
BPH-715
RACHEL PETKEWICH
at the Priestley House at 7 PM on April 9, when stakeholders may voice their concerns. But Amanda Kessler, director of the nonprofit Friends of Joseph Priestley House (FJPH), feels blindsided by the PHMC closure recommendation. She says her group, which helps operate and raise money for the site, hasn’t been given enough notice to find alternatives to state funding. “I hope they follow through,” Kessler says of Franco’s search for solutions. “Actions speak louder than words.” Both organizations have looked to ACS for help. The PHMC internal review, for example, suggests that FJPH should enter a management agreement with ACS and Pennsylvania State University to manage the Priestley House. But ACS is noncommittal at this stage. ACS Director of Public Affairs Glenn S. Ruskin says his office is working with society members in Pennsylvania to make sure there is a strong show of support at the April 9 meeting to keep the site open. “We want to see if we can reverse the PHMC decision,” Ruskin says. “Would ACS support the site if it is closed? I don’t know. That would have to be decided further down the road.”—WILLIAM SCHULZ
WWW.CEN-ONLINE.ORG
ACS
BETTER BISPHOSPHONATES
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The Joseph Priestley House in Northumberland, Pa.
