Topics in Heterocyclic Chemistry, v.15. Bioactive Heterocycles VI. Flavonoids and Anthocyanins in Plants, and Latest Bioactive Heterocycles I, 2008, p.290

290 Pages·2008·5.88 MB·English

by  Noboru Motohashi.

15
Topics in Heterocyclic Chemistry
SeriesEditor:R.R.Gupta
EditorialBoard:
D.Enders·S.V.Ley·G.Mehta·K.C.Nicolaou
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TopicsinHeterocyclicChemistry
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Volume1,2006
Bioactive Heterocycles VI
FlavonoidsandAnthocyaninsinPlants,
andLatestBioactiveHeterocyclesI
Volume Editor: NoboruMotohashi
Withcontributionsby
J.Bariwal·A.Dasgupta·S.G.Dastidar·J.Deli·R.Didiziapetris
H.Engi·M.P.Gangeenahalli·N.Gyémánt·J.Hohmann·M.Inabe
M.Ishihara·S.Jaldappagari·M.Kawase·H.Kikuchi·M.Kobayashi
L.Krenn·T.Kurihara·J.Molnár·N.Motohashi·J.H.Naismith
Y.Nakamura·I.Ocsovski·H.Sakagami·Z.Schelz·A.Shah
K.Shinohara·Y.Shirataki·G.Spengler·M.Szabo·M.Szücs
L.Tanács·H.Wakabayashi
123
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ISBN978-3-540-79217-8 e-ISBN978-3-540-79218-5
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Preface
AspartoftheseriesTopicsinHeterocyclicChemistry,thisvolumetitledBioac-
tiveHeterocyclesIIpresentscomprehensiveandup-to-datereviewsonselected
topicsconcerningflavonoidsandanthocyaninsinplants,andheterocyclessuch
asbioactivephenothiazines, phenoxazines, andrelatedcompounds.Thevol-
umeisseparatedintotwosectionsmainlyconcentratingonthesetwotopics.
There areabundant anddiverse flavonoidswithcarbohydratesandlipids,
alkaloids (betalain alkaloids and other alkaloids), phenols (chromones,cou-
marins,lignans,quinines,andotherphenolics),terpenoids(monoterpenoids,
sesquiterpene lactones, triperpenoid saponins, carotenoids, and other ter-
penoids),andmineralsasmicronutritionalphytochemicalsinfruitsandveg-
etables of our daily diets. Among these phytochemicals, the flavonoids have
specificfunctionalityinrelationtoage-relateddiseasessuchashypertension,
diabetes,cardiacinfarction,cataracts,andcancer.Theauthorsofeachchapter
inthefirstsectionhavepresentedtheirevidenceinrelationtothemechanism
ofthepreventativeandtherapeuticabilityofthecompounds.
Thefirstchapter,“FunctionalityofAnthocyaninsasAlternativeMedicine”
byNoboruMotohashiandHiroshiSakagami,presentstheirantioxidantmech-
anismforanthocyanidins, whicharepresentincommonfoods.Itispossible
that anthocyanins may have been used both preventatively and clinically as
partofmany“folkloremedicines”worldwideandmayhaveprovidedhealth-
carebenefitssincetheappearanceofmankindsome7.5millionyearsago.The
reviewwillinformthereaderastotheirfunctionalityandmechanism.
Thesecondchapter,“BioactiveMechanismofInteractionbetweenAntho-
cyaninsandMacromoleculesLikeDNAandProteins”bySeetharamappaJal-
dappagari,NoboruMotohashi,MamathaP.Gangeenahalli,andJamesH.Nai-
smith,presentsthebiologicalactivitiesofanthocyanins,andtheinteractions
ofanthocyanins withDNA and protein. Anthocyanins might protectagainst
damagetohealthbysometypesofharmfuloxidantsthroughvariousmech-
anisms such as their antioxidative activity, protein active site binding, and
chelating complexformation. The review presents theinteresting interactive
mechanismofanthocyanin–DNAcomplexformation.
The thirdchapter,“Antibacterial ActivityofArtificial Phenothiazines and
IsoflavonesfromPlants”byAsishDasgupta,SujataGhoshDastidar,Yoshiaki
Shirataki,andNoboruMotohashi,presentsthatsyntheticphenothiazinesand
X Preface
isoflavononesare not only powerful antibacterial agents as revealed by their
activityintestswithhundreds ofbacteria, butoftenalsoactasantiviraland
anticancer agents. Many such compounds can eliminate drug-resistant plas-
midsandactivelyparticipateininhibitionofeffluxpumpsinpathogens.This
studyhasopenedupanewdomaininthefieldofantimicrobialchemotherapy
sincethesecompoundscanbeadministeredinhumansstraightawayormay
befurtherimprovedbystructuralmodifications.
Thefourthchapter,“InhibitionofMultidrugResistanceofCancerCellsby
SelectedCarotenoids,FlavonoidsandAnthocyanins”byJosephMolnár,Helga
Engi, Nóra Gyémánt, Zsuzsanna Schelz, Gabriella Spengler, Imre Ocsovszki,
Miklós Szücs, Judith Hohmann, Margaret Szabó, Lajos Tanács, Péter Mol-
nár, Joseph Deli, Liselotte Krenn, Masami Kawase, Hidetsugu Wakabayashi,
Teruo Kurihara, Yoshiaki Shirataki, Hiroshi Sakagami, Noboru Motohashi,
and Remigijus Didiziapetris, tried to indirectly define receptor-structure in
the presence of the diverse structurally unrelated carotenoids, flavonoids,
isoflavonoids,andterpenoids.Thisreviewmaycontributetostudiesofmulti-
drug-resistant(MDR)proteinsthatbelongtotheATP-bindingcassettesuper-
familywhicharepresentinamajorityofhumantumorsandareanimportant
finalcauseoftherapeuticfailure.
Thefifthchapter,“ChangesinPolyamineLevelsduringCellDeathInduced
byHeterocycles”byMasakiKobayashi,HiroshiSakagami,MasamiKawase,and
NoboruMotohashi,presentschangesinpolyaminelevelsduringcelldeathin-
duced by selective properties of diverse heterocycles such as phenoxazines,
flavonoids, and other heterocycles. Natural polyamines (putrescine, spermi-
dine, spermine) are aliphatic amines containing two or more amino groups,
whichplayimportantrolesinregulating cellgrowthanddifferentiation. De-
pletion of polyamine in cells has been known to inhibit cell proliferation or
induce celldeath. This review might helpthe studyofchangesin polyamine
levelsoncelldeathwheninducedbyheterocycles.
Inthesecondsectionofthevolume,N-heterocyclessuchasphenothiazines,
phenoxazines, dihydropyridines, and related compounds are shown also to
have interesting biological activity including antitumor activity, vermicide,
antibacterial activity, and antischizophrenic activity (i.e. chlorpromazine of
thephenothiazinefamilyanditsanalogs).Theactivityofphenothiazineand
compounds such as phenoxazines and related heterocycles, and also recent
bioactivemesoionicheterocycleswillbediscussed.
The sixth chapter, “Tumor-Specificity and Type of Cell Death Induced by
Heterocycles”by HiroshiSakagami, Masaki Kobayashi, Mariko Ishihara, Hi-
rotaka Kikuchi, Yukio Nakamura, Masami Kawase, and Noboru Motohashi,
presents the tumor specificities of trifluoromethylimidazoles, phenoxazines,
3-formylchromonederivatives, coumarinanditsderivatives, andvitaminK
2
derivatives andthetypeofcelldeathinduced bythese heterocycles. Thisre-
view might beneficially establish a definitive strategy for the exploration of
newhighlytumor-selectivecompounds.Also,thescreeningprocessofhighly
Preface XI
tumor-specific compounds should be introduced before the identification of
thetypeofcelldeath(either apoptosis, autophagy, ornecrosis)and thecell-
deathinductionmechanism.
Theseventhchapter,“AdvancedDihydropyridinesasNovelMultidrugRe-
sistanceModifiersandReversing Agents”byAnamikShah,Jitender Bariwal,
Joseph Molnár, Masami Kawase, and Noboru Motohashi, presents a com-
prehensive review of their synthetic methodologyfor the preparation of the
most-activeP-glycoprotein(Pgp)inhibitordihydropyridine.These“privilege
structured” families of compounds are potent inhibitors of P-glycoprotein,
whicharethemaincauseofeffluxoftoxinsfromthecells.Thisreviewmight
beusefulforexploratoryfuturedrug development duetothePgpinhibitory
propertyofthedihydropyridines.
Thelastchapter,“TheoreticalStudiesonPhenothiazines,Benzo[a]pheno-
thiazinesandBenz[c]acridines”byTeruoKurihara,KazumiShinohara,Hidet-
sugu Wakabayashi, Noboru Motohashi, Hiroshi Sakagami, and Joseph Mol-
nár, presents their quantitative structure–activity relationship (QSAR) anal-
ysis for minimum inhibitory concentration (MIC) of phenothiazines and
benzo[a]phenothiazines. The MIC values of phenothiazines were well cor-
relatedto∆∆Hf,HOMOenergy,andµG.QSARmaybeapplicabletopredict
theMICofphenothiazines. Thisreviewcouldcontributetopredictionofthe
relationshipofstructuretobiologicalactivity.
Itishopedthatthisvolumewillserveasastimulusforresearcherswithan
interest in the field of biologicalactivity of flavonoids and heterocycles, and
alsostimulatefurtherdevelopmentfornoveltherapeutics.
Tokyo,March2008 NoboruMotohashi