Toxicity-structure activity evaluation of limonoids from Swietenia species on Artemia salina.

CONTEXT: 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. MATERIALS AND 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. DISCUSSION AND CONCLUSIONS: Toxicity can be improved via semisynthesis. The compounds exhibiting high toxicity (low LC(50)) may be good candidates for cytotoxicity studies.

Limonoids from Meliaceae with lipid peroxidation inhibitory activity.

In this study the antioxidant activity of natural limonoids from Meliaceae swietenolide (1), 3,6-O,O-diacetylswietenolide (2), swietenine (3), swietemahonin G (4) and 2-hydroxyswietenine (5) were investigated along with the semi-synthetic analogues (6-25) of compounds 1, 3-4. Lipid peroxidation (LPO) inhibitory assays revealed 85.6, 13.3, 77.3, 61.2 and 24.6% inhibition for the natural compounds 1-5. Excellent antioxidant activity was seen for the semi-synthetic analogues 10 (98.3%), 16-17, 21-22 and 25 (100%), which were more active than the positive controls BHA (91.3%) and TBHQ (95.7%).