title: Toxicity-structure activity evaluation of limonoids from Swietenia species on Artemia salina.
abstract: BACKGROUND
  Many plant extracts and compounds are being investigated for their cytotoxicity and hence their medicinal or therapeutic properties. Reports of toxicity studies with limonoid analogs have been sparse and have involved mainly crude extracts. In this study, individual natural limonoids have been isolated and their toxicity manipulated via semisynthesis.
  
  
  OBJECTIVE
  The lethality of limonoid analogs from Swietenia macrophylla King and Swietenia aubrevilleana Stehlé & Cusin (Meliaceae) against Artemia salina Leach was determined.
  
  
  METHODS
  Four known natural limonoids were isolated from the dry ground seeds of S. macrophylla and S. aubrevilleana, modified using acylation and hydrolysis reactions and tested in A. salina lethality assays at 1-400 ppm. A 50% lethal concentration (LC(50)) was determined by probit analysis.
  
  
  RESULTS
  Higher levels of toxicity were achieved in most of the prepared analogs compared with the parent natural limonoids. The compound showing the highest toxicity with LC(50) 3.9 ppm was 3-O-benzoyl-3-detigloylisoswietenine (20). Other analogs with high toxicity were 6-O-benzoylswietenolide (7), 6-O-benzoylswietenine (17), and 3,6-O,O-dipropionylswietenolide (9), which showed LC(50) values of 4.3, 7.5, and 28.5 ppm, respectively.
  
  
  CONCLUSIONS
  Toxicity can be improved via semisynthesis. The compounds exhibiting high toxicity (low LC(50)) may be good candidates for cytotoxicity studies.
authors.affiliation: Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada. robert.fowles@ualberta.ca
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fowles
authors.forename: Baldwin S
authors.initials: BS
authors.lastname: Mootoo
authors.forename: Russel S
authors.initials: RS
authors.lastname: Ramsewak
authors.forename: Ayub
authors.initials: A
authors.lastname: Khan
mesh_terms: D000818:Animals; D001156:Artemia / Q000187:drug effects*; D007928:Lethal Dose 50; D036701:Limonins / Q000737:chemistry / Q000302:isolation & purification / Q000633:toxicity*; D029582:Meliaceae / Q000737:chemistry*; D012639:Seeds; D013329:Structure-Activity Relationship
chemical_list: D036701:Limonins