title: Cytotoxicity, nitric oxide and acetylcholinesterase inhibitory activity of three limonoids isolated from Trichilia welwitschii (Meliaceae).
abstract: BACKGROUND
  Limonoids are highly oxygenated compounds with a prototypical structure. Their occurrence in the plant kingdom is mainly confined to plant families of Meliaceae and Rutaceae. Owing to their wide range of pharmacological and therapeutic properties, this study was aimed at investigating the potential nitric oxide (NO) and acetylcholinesterase (AChE) inhibitory activity and the cytotoxicity of three limonoids: trichilia lactone D5 (1), rohituka 3 (2) and dregeanin DM4 (3), isolated from Trichilia welwitschii C.DC.
  
  
  RESULTS
  Results indicated that the three limonoids had low cytotoxicity towards Vero cells with LC50 values ranging from 89.17 to 75.82 μg/mL. Compounds (2) and (3) had lower cytotoxicity compared to puromycin and doxorubicin used as reference cytotoxic compounds. Compound (1) (LC50 of 23.55 μg/mL) had good antiproliferative activity against RAW 264.7 cancer cells. At the lowest concentration tested (0.5 µg/mL), compound (2) and (3) released the lowest amount of nitric oxide (2.97 and 2.93 µM, respectively). The three limonoids had anti-AChE activity with IC50 values ranged of 19.13 μg/mL for (1), 34.15 μg/mL for (2) and 45.66 μg/mL for (3), compared to galantamine (IC50 of 8.22 μg/mL) used as positive control.
  
  
  CONCLUSIONS
  The limonoid compounds studied in this work inhibited nitric oxide production in LPS-stimulated macrophages and had anti-AChE activity. Trichilia lactone D5 had potential antiproliferative activity against RAW 264.7 cancer cells. The limonoids had low cytotoxicity towards Vero cells lines. This study provided further examples of the importance of limonoids compounds as potential AChE inhibitors and anti-inflammatory agents targeting the inhibition of NO production.
authors.affiliation: Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, 0110, South Africa. jpdzoyem@yahoo.fr.|Department of Biochemistry, Faculty of Science, University of Dschang, P.O. Box 67, Dschang, Cameroon. jpdzoyem@yahoo.fr.
authors.forename: Jean P
authors.initials: JP
authors.lastname: Dzoyem
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. armelletsamo@yahoo.fr.
authors.forename: Armelle T
authors.initials: AT
authors.lastname: Tsamo
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. raduismelong@yahoo.fr.
authors.forename: Raduis
authors.initials: R
authors.lastname: Melong
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. mpierrendi@yahoo.fr.
authors.forename: Pierre
authors.initials: P
authors.lastname: Mkounga
authors.affiliation: Department of Organic Chemistry, Faculty of Science, University of Yaoundé I, P.O. Box 812, Yaoundé, Cameroon. ankengf@yahoo.fr.
authors.forename: Augustin E
authors.initials: AE
authors.lastname: Nkengfack
authors.affiliation: Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, 0110, South Africa. lyndy.mcgaw@up.ac.za.
authors.forename: Lyndy J
authors.initials: LJ
authors.lastname: McGaw
authors.affiliation: Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort, Pretoria, 0110, South Africa. kobus.eloff@up.ac.za.
authors.forename: Jacobus N
authors.initials: JN
authors.lastname: Eloff
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000032:analysis / Q000494:pharmacology; D007928:Lethal Dose 50; D036701:Limonins / Q000032:analysis / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D009569:Nitric Oxide / Q000032:analysis / Q000037:antagonists & inhibitors*; D000067996:RAW 264.7 Cells; D014709:Vero Cells
chemical_list: D000893:Anti-Inflammatory Agents; D002800:Cholinesterase Inhibitors; D007783:Lactones; D036701:Limonins; D008070:Lipopolysaccharides; D009569:Nitric Oxide; C105839:rohitukin