The ability of eleven known flavonoids isolated from Nectandra amazonum (Lauraceae) was tested for in vitro PGHS (COX) inhibition. All test compounds exhibited a dose dependent activity at different levels, exhibiting selectivity towards COX-1 inhibition. Autodock Vina was used to dock the compound structures within the active site of the PGHS-1 (PDB: 3N8V). In vitro results showed that chalcone and dihydrochalcone-related compounds exhibited reasonable inhibitory properties (IC50: 1.56-36.5 μM), with good correlation with docking results. Arg120 (or Tyr355) and Ser530 were found to be the key residues to dock the most active flavonoids, indicating such interaction might interfere with the formation of prostaglandin H2 in the active site of COX-1.
JacksonLM, WuKC, MahidaYR, JenkinsD, HawkeyCJ. (2000) Cyclooxygenase (COX) 1 and 2 in normal, inflamed, and ulcerated human gastric mucosa. Gut, 47, 762–770.
2.
Van HeckenA, SchwartzJI, DepréM, De LepeleireI, DallobA, TanakaW, WynantsK, BuntinxA, ArnoutJ, WongPH, EbelDL, GertzBJ, De SchepperPJ. (2000) Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers. Journal of clinical pharmacology, 40, 1109–1120.
3.
CharlierC, MichauxC. (2003) Dual inhibition of cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) as a new strategy to provide safer non-steroidal anti-inflammatory drugs. European Journal of Medicinal Chemistry, 38, 645–659.
4.
KonstamMA, WeirMR, ReicinA, ShapiroD, SperlingRS, BarrE, GertzBJ. (2001) Cardiovascular thrombotic events in controlled, clinical trials of rofecoxib. Circulation, 104, 2280–2288.
5.
VaneJR, BakhleYS, BottingRM. (1998) Cyclooxygenases 1 and 2. Annual Review of Pharmacology and Toxicology, 38, 97–120.
6.
BombardierC, LaineL, ReicinA, ShapiroD, Burgos-VargasR, DavisB, DayR, Bosi-FerrazM, HawkeyCJ, HochbergMC, KvienTK, SchnitzerTJ. (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. The New England Journal of Medicine, 343, 1520–1528.
7.
LinCT, ChuFH, TsengYH, TsaiJB, ChangST, WangSY. (2007) Bioactivity investigation of Lauraceae trees grown in Taiwan. Pharmaceutical Biology, 45, 638–644.
8.
Da Silva-FilhoAA, AndradeE, SilvaML, CarvalhoJCT, BastosJK. (2004) Evaluation of analgesic and anti-inflammatory activities of Nectandra megapotamica (Lauraceae) in mice and rats. The Journal of Pharmacy and Pharmacology, 56, 1179–1184.
9.
AdeyemiOO, OkpoSO, OguntiOO. (2002) Analgesic and anti-inflammatory effects of the aqueous extract of leaves of Per sea americana Mill (Lauraceae). Fitoterapia, 73, 375–380.
ZschockeS, van StadenJ, PaulusK, BauerR, HornMM, MunroOQ, BrownNJ, DrewesSE. (2000). Stereostructure and anti-inflammatory activity of three diastereomers of ocobullenone from Ocotea bullata. Phytochemistry, 54, 591–595.
12.
LinH-Y, ChangS-T. (2012) Kaempferol glycosides from the twigs of Cinnamomum osmophloeum and their nitric oxide production inhibitory activities. Carbohydrate Research, 364, 49–53.
ChiYS, JongHG, SonKH, ChangHW, KangSS, KimHP. (2001) Effects of naturally occurring prenylated flavonoids on enzymes metabolizing arachidonic acid: Cyclooxygenases and lipoxygenases. Biochemical Pharmacology, 62, 1185–1191.
15.
WuCM, WuSC, ChungWJ, LinHC, ChenKT, ChenYC, HsuMF, YangJM, WangJP, LinCN. (2007) Antiplatelet effect and selective binding to cyclooxygenase (COX) by molecular docking analysis of flavonoids and lignans. International Journal of Molecular Sciences, 8, 830–841.
16.
AwangK, AbdullahZ, MukhtarMR, LitaudonM, JaafarFM, HadiAHA, ThomasNF. (2009) Dunaliine A, a new amino diketone from Desmos dunalii (Annonaceae). Natural Product Research, 23, 652–658.
17.
SeidelV, BailleulF, WatermanPG. (2000). (Rel)-lβ,2α-di-(2,4-dihydroxy-6-methoxybenzoyl)-3β, 4α-di-(4-methoxyphenyl)-cyclobutane and other flavonoids from the aerial parts of Goniothalamus gardneri and Goniothalamus thwaitesii. Phytochemistry, 55, 439–446.
18.
EconomidesC, AdamKP. (1998) Lipophilic flavonoids from the fern Woodsia scopulina. Phytochemistry, 49, 859–862.
19.
VeitchNC, SuttonPSE, KiteGC, IrelandHE. (2003) Six new isoflavones and a 5-deoxyflavonol glycoside from the leaves of Ateleia herbert-smithii. Journal of Natural Products, 66, 210–216.
20.
BatterhamTJ, HighetRJ. (1964) Nuclear magnetic resonance spectra of flavonoids. Australian Journal of Chemistry, 17, 428–439.
21.
BickIC, BrownR, HillisW. (1972) Three flavanones from leaves of Eucalyptus sieberi. Australian Journal of Chemistry, 25, 449–451.
22.
ThuyTTT, QuanTD, AnhNTH, Van SungT. (2011) A new hydrochalcone from Miliusa sinensis. Natural Product Research, 25, 1361–1365.
UmbetovaAK, EsirkegenovaSZ, ChaudriIM, OmurkamzinovaVB, AbilovZA. (2004). Flavonoids of plants from the genus Tamarix. Chemistry of Natural Compounds, 40, 297–298.
25.
RaoPNP, AminiM, LiH, HabeebAG, KnausEE. (2003) Design, synthesis, and biological evaluation of 6-substituted-3-(4-methanesulfonylphenyl)-4-phenylpyran-2-ones: a novel class of diarylheterocyclic selective cyclooxygenase-2 inhibitors. Journal of Medicinal Chemistry, 46, 4872–4882.
26.
SeeligerD, de GrootBL. (2010) Ligand docking and binding site analysis with PyMOL and Autodock/Vina. Journal of Computer-Aided Molecular Design, 24, 417–422.
27.
SidhuRS, LeeJY, YuanC, SmithWL. (2010) Comparison of cyclooxygenase-1 crystal structures: cross-talk between monomers comprising cyclooxygenase-1 homodimers. Biochemistry, 49, 7069–7079.
28.
DewarM, ZoebischE, HealyE, StewartJ. (1985) AM1: a new general purpose quantum mechanical molecular model. Journal of American Chemical Society, 107, 3902–3909.
29.
BeckeAD. (1993) Density-Functional Thermochemistry. III. The role of exact exchange. Journal of Chemical Physics, 98, 5648–5652.
