Abstract
Drug-resistant Staphylococcus aureus is a continuing public health concern, both in the hospital and community settings. Antibacterial compounds that possess novel structural scaffolds and are effective against multiple S. aureus strains, including current drug-resistant ones, are needed. Previously, we have described the chrysophaentins, a family of bisdiarylbutene macrocycles from the chrysophyte alga Chrysophaeum taylori that inhibit the growth of S. aureus and methicillin-resistant S. aureus (MRSA). In this study we have analyzed the geographic variability of chrysophaentin production in C. taylori located at different sites on the island of St. John, U.S. Virgin Islands, and identified two new linear chrysophaentin analogs, E2 and E3. In addition, we have expanded the structure activity relationship through synthesis of fragments comprising conserved portions of the chrysophaentins, and determined the antimicrobial activity of natural chrysophaentins and their synthetic analogs against five diverse S. aureus strains. We find that the chrysophaentins show similar activity against all S. aureus strains, regardless of their drug sensitivity profiles. The synthetic chrysophaentin fragments indeed mimic the natural compounds in their spectrum of antibacterial activity, and therefore represent logical starting points for future medicinal chemistry studies of the natural products and their analogs.
Highlights
Staphylococcus aureus has long been a public health concern, and is currently the leading cause of skin, soft tissue, bloodstream, and lower respiratory tract bacterial infections [1]
The original chrysophaentins came from one collection of C. taylori made in Round Bay, located on the southern side of St
The rare marine chrysophyte alga C. taylori has yielded a number of biologically active natural products
Summary
Staphylococcus aureus has long been a public health concern, and is currently the leading cause of skin, soft tissue, bloodstream, and lower respiratory tract bacterial infections [1]. Penicillin was discovered in 1928 and first used in 1941, but by the late 1940’s was ineffective due to the rise in penicillinase-producing S. aureus [2,3]. In the late 1980s and 1990s, the proportion of methicillin resistant infections rose significantly compared to susceptible ones worldwide [6]. In the United States, S. aureus is the leading cause of hospital-acquired infections [7]. Most of these strains are methicillin-resistant, and in the early 2000’s, more patients in the U.S succumbed to lethal MRSA infections than to AIDS, tuberculosis, and hepatitis B combined [8]
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