Ent-kaur-16(17)-en-19-oic acid (kaurenoic acid, KA) is a tetracyclic diterpene prototype for natural anticaries agents. Six KA derivatives were prepared and their antimicrobial activity against the main microorganisms involved in the caries process evaluated. The sodium salt of KA (KA-Na) was the most active, displaying very promising MIC values for most pathogens. Time-kill assays against the primary causative agent of caries (Streptococcus mutans) indicated that KA and KA-Na only inhibited growth in the first 12 h, suggesting a bacteriostatic effect. After this period (12-24 h), their bactericidal effect was clearly noted. KA and KA-Na showed no synergy when combined with the gold standard anticariogenic (chlorhexidine dihydrochloride, CHD) in the checkerboard assays against S. mutans.
AllakerR.P., DouglasC.W.I. (2009) Novel antimicrobial therapies for dental plaque-related diseases. International Journal of Antimicrobial Agents, 33, 8–13.
2.
AmbrosioS.R., FurtadoNAJC, De OliveiraD.C.R., Da CostaF.B., MartinsC.H.G., De CarvalhoT.C., PortoT.S., VenezianiR.C.S. (2008) Antimicrobial activity of kaurane diterpenes against oral pathogens. Zeitschrift Fur Naturforschung Section C-a Journal of Biosciences, 63c, 326–330.
3.
LimebackH. (1999) A re-examination of the pre-eruptive and post-eruptive mechanism of the anticaries effects of fluoride: is there any anticaries benefit from swallowing fluoride?Community Dentistry and Oral Epidemiology, 27, 62–71.
4.
HaffajeeA.D., YaskellT., SocranskySS., (2008) Antimicrobial Effectiveness of an Herbal Mouthrinse Compared With an Essential Oil and a Chlorhexidine Mouthrinse. Journal of the American Dental Association, 139, 606–611.
5.
TsuiV.W.K., WongR.W.K., RabieA.B.M. (2008) The inhibitory effects of naringrin on the growth of periodontal pathogens in vitro. Phytotherapy Research, 22, 401–406.
6.
GreenbergM., DoddsM., TianM. (2008) Naturally occurring phenolic antibacterial compounds show effectiveness against oral bacteria by a quantitative structure-activity relationship study. Journal of Agricultural and Food Chemistry, 56, 11151–11156.
7.
MoreG., TshikalangeT.E., LallN., BothaF., MeyerJ.J.M. (2008) Antimicrobial activity of medicinal plants against oral microorganisms. Journal of Ethnopharmacology, 119, 473–477.
8.
PortoT.S., RangelR., FurtadoN., de CarvalhoT.C., MartinsC.H.G., VenezianiR.C.S., Da CostaF.B., VinholisA.H.C., CunhaW.R., HelenoV.C.G., AmbrosioS.R. (2009) Pimarane-type Diterpenes: Antimicrobial Activity against Oral Pathogens. Molecules, 14, 191–199.
9.
SaleemM., NazirM., AliM.S., HussainH., LeeY.S., RiazN., JabbarA. (2010) Antimicrobial natural products: an update on future antibiotic drug candidates. Natural Product Reports, 27, 238–254.
WhiteR.L., BurgessD.S., ManduruM., BossoJ.A. (1996) Comparison of three different in vitro methods of detecting synergy: time-kill, checkerboard, and E test. Antimicrobial Agents and Chemotherapy, 40, 1914–1918.
12.
PelletierS.W., ChokshiH.P., DesaiH.K. (1986) Separation of diterpenoid alkaloid mixtures using vacuum liquid chromatography. Journal of Natural Products, 49, 892–900.
13.
Do NascimentoA.M., De OliveiraD.C.R. (2001) Kaurene Diterpenes and Other Chemical Constituents from Mikania stipulacea (M. Vahl) Willd. Journal of Brazilian Chemical Society, 12, 552–555.
14.
DalóN.L., Sosa-SequeraM.C., UsubillagaA. (2007) On the anticonvulsivant activity of kaurenic acid. Investigación Clínica, 48, 349–358.
15.
BatistaR., GarciaP.A., CastroM.A., Del CorralJ.M.M., FelicianoA.S., De OliveiraA.B. (2007) New oxidized ent-kaurane and ent-norkaurane derivatives from kaurenoic acid. Journal of the Brazilian Chemical Society, 18, 622–627.
16.
BoeckP., SaM.M., de SouzaB.S., CercenaR., EscalanteA.M., ZachinoS.A., CechinelV., YunesR.A. (2005) A simple synthesis of kaurenoic esters and other derivatives and evaluation of their antifungal activity. Journal of the Brazilian Chemical Society, 16, 1360–1366.
17.
CrossB.E., HansonJ.R., GaltR.H.B. (1963) New metabolites of Giberella Fujikuroi.3. Structure of 7-Hydroxykaurenolide. Journal of the Chemical Society, 2944–2961.
18.
FragaB.M., HernandezM.G., RodriguezM.D., DiazC.E., GonzalezP., HansonJ.R. (1987) Transformation of ent-kaur-15-enes by Gibberella Fujikuroi. Phytochemistry, 26, 1931–1934.
19.
PiozziF., VenturelP., BellinoA., MarinoM.L. (1973) Patial synthesis of ent-kaur-16-ene-15Beta,18-diol and ent-kaur-16-ene-7alpha, 15Beta, 18-triol. Journal of the Chemical Society-Perkin Transactions1, 1164–1166.
20.
NCCLS. (2003) National Comittee for Clinical Laboratory Standars (NCCLS) document M7-A6 - Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically.
21.
PalominoJ.C., MartinA., CamachoM., GuerraH., SwingsJ., PortaelsF. (2002) Resazurin microtiter assay plate: Simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrobial Agents and Chemotherapy, 46, 2720–2722.
22.
D'ArrigoM., GinestraG., MandalariG., FurneriP.M., BisignanoG. (2010) Synergism and postantibiotic effect of tobramycin and Melaleuca alternifolia (tea tree) oil against Staphylococcus aureus and Escherichia coli. Phytomedicine, 17, 317–322.
