Scalarane sesterterpenoids: semisynthesis and biological activity.
Aiming to improve the potency and selectivity of scalarane sesterterpenoids, a series of natural and semisynthetic analogues, derived from the cytotoxic naturally abundant sesterterpene heteronemin (1), were evaluated for their in vitro antimicrobial and cytotoxic properties. The new sesterterpenes 16-O-methylsesterstatin 4 (6c), 17, 24-dihydroheteronemin (7a), 16, 25-deacetoxy-17, 24-dihydroheteronemin (7b), and 16-deacetoxy-25-methoxy-17, 24-dihydroheteronemin (7c) were structurally defined via physical data analyses. Scalarane sesterterpenes possessing an unsaturated 1,4-dialdehyde moiety showed potent inhibitory activity against methicillin-resistant Staphylococcus aureus at concentrations that are not significantly cytotoxic to mammalian cells. The structural features for the cytotoxicity of scalarane sesterterpenoids are discussed.
Kamel
Haidy N
HN
Departments of Pharmacognosy and Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, University of Mississippi, University, Mississippi 38677, USA.
Kim
Young B
YB
Rimoldi
John M
JM
Fronczek
Frank R
FR
Ferreira
Daneel
D
Slattery
Marc
M
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D015269:Mycobacterium avium Complex / Q000187:drug effects; D011161:Porifera / Q000737:chemistry; D054830:Sesterterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013729:Terpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D054830:Sesterterpenes; D013729:Terpenes; C493748:heteronemin