title: Fatty acid synthase inhibitors from plants: isolation, structure elucidation, and SAR studies.
abstract: Fatty acid synthase (FAS) has been identified as a potential antifungal target. FAS prepared from Saccharomyces cerevisiae was employed for bioactivity-guided fractionation of Chlorophora tinctoria,Paspalum conjugatum, Symphonia globulifera, Buchenavia parviflora, and Miconia pilgeriana. Thirteen compounds (1-13), including three new natural products (1, 4, 12), were isolated and their structures identified by spectroscopic interpretation. They represented five chemotypes, namely, isoflavones, flavones, biflavonoids, hydrolyzable tannin-related derivatives, and triterpenoids. 3'-Formylgenistein (1) and ellagic acid 4-O-alpha-l-rhamnopyranoside (9) were the most potent compounds against FAS, with IC(50) values of 2.3 and 7.5 microg/mL, respectively. Furthermore, 43 (14-56) analogues of the five chemotypes from our natural product repository and commercial sources were tested for their FAS inhibitory activity. Structure-activity relationships for some chemotypes were investigated. All these compounds were further evaluated for antifungal activity against Candida albicans and Cryptococcus neoformans. Although there were several antifungal compounds in the set, correlation between the FAS inhibitory activity and antifungal activity could not be defined.
authors.affiliation: National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, Department of Pharmacognosy, School of Pharmacy, The University of Mississippi, University, MS 38677, USA. xli@olemiss.edu
authors.forename: Xing-Cong
authors.initials: XC
authors.lastname: Li
authors.forename: Alpana S
authors.initials: AS
authors.lastname: Joshi
authors.forename: Hala N
authors.initials: HN
authors.lastname: ElSohly
authors.forename: Shabana I
authors.initials: SI
authors.lastname: Khan
authors.forename: Melissa R
authors.initials: MR
authors.lastname: Jacob
authors.forename: Zhizheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Daneel
authors.initials: D
authors.lastname: Ferreira
authors.forename: Larry A
authors.initials: LA
authors.lastname: Walker
authors.forename: Sheldon E
authors.initials: SE
authors.lastname: Broedel
authors.forename: Robert E
authors.initials: RE
authors.lastname: Raulli
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Cihlar
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D029764:Combretaceae / Q000737:chemistry; D003455:Cryptococcus neoformans / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D020128:Inhibitory Concentration 50; D007529:Isoflavones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D035322:Melastomataceae / Q000737:chemistry; D015394:Molecular Structure; D029586:Moraceae / Q000737:chemistry; D031781:Paspalum / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D013329:Structure-Activity Relationship; D013634:Tannins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D004791:Enzyme Inhibitors; D007529:Isoflavones; D013634:Tannins; D014315:Triterpenes; D064429:Fatty Acid Synthases