Ntu 3: Kev Ua Haujlwm Zoo Tshaj Plaws Ntawm Ntuj Phenols Los Txhim Kho Kev Ua Txhaum Cai

Yog xav paub ntxiv. tiv taujtina.xiang@wecistanche.com

5. Lipidic Phenols

Lipidicphenols(los yog phenolic lipids, tseem hu ua phenolipids) yog phenols hloov nrog lipophilic chains, uas ua rau cov molecule amphiphilic yam ntxwv. Ib qho tseem ceeb phenolic lipid yog -tocoferol [330]; Txawm li cas los xij, qhov sib xyaw no ib leeg tsim nyog rau kev tshuaj xyuas, yog li nws tsis tau suav nrog.

Qhov tseem ceeb ntawm natural lipidic phenols tau underestimated rau lub sij hawm ntev [331]. Txawm li cas los xij, lawv zoo heevantioxidant, antigenotoxic, thiab cytostatic zog yog tam sim no tsim [332], nrog rau lawv cov bioactivity nyob rau hauv cuam tshuam txoj kev lom neeg koom nrog hauvAlzheimer tus kab mobpathogenesis 333]. Kev tiv thaiv kab mob thiab tiv thaiv kev mob caj dab kuj tau tshaj tawm rau lipidic phenols muab rho tawm los ntawm cov txiv ntoo txiv ntoo (Anacardium occidentale) [334].

Vim hais tias ntawm qhov tseem ceeb ntawm cov chav kawm ntawm cov tebchaw, ob peb hluavtaws lipidic phenols tau raug npaj nyob rau hauv kaum xyoo tsis ntev los no los txuas ntxiv lawv cov kev siv tshuaj lom neeg.

Nyem qhov no kom paub ntau yam khoom

5.1. Biocatalyzed Syntheses ntawm Lipidic Phenols

Lipases yog cov enzymes xaiv los ua cov tshuaj tiv thaiv transesterification kom tau txais kev hloov kho lossis hluavtaws lipids, nrog rau kev ua haujlwm lossis kev siv tshuaj [335,336]. Ib tug loj tus naj npawb ntawm esters los ntawm catechol thiab fatty acids tau npaj mus do ib tug ncua kev kawm ntawv ntawm catechol nyob rau hauv ethyl ester ntawm ib tug fatty acid [337].

Semisynthetic lipidic phenols tau npaj los ntawm kev hloov pauv cov tshuaj phenolic acids nrog cov roj flaxseed [338,339], olein [340], ntses siab roj [341], thiab krill roj [342]. Cov tshuaj tiv thaiv, ua nyob rau hauv cov kuab tshuaj organic los yog nyob rau hauv ib tug hnyav-free system [343,344], tau catalyzed los ntawm Novozym 435 cais los ntawm Candida Antarctica (Scheme 33).

Tsis ntev los no, yields txhim kho siv supercritical carbon dioxide raws li cov tshuaj tiv thaiv nruab nrab [345]. Cov kev npaj sib xyaw ntawm lipidic phenols tau sim rau kev ua haujlwm antioxidant. Qhov tau txais radical scavenging kev ua ub no los ntawm nruab nrab mus rau qhov zoo, tab sis nws yeej ib txwm qis dua li ntawm -tocopherol. Ntxiv mus, tau los ntawm kev sib tov, cov txiaj ntsig tsis tuaj yeem raug ntaus nqi rau ib qho kev sib xyaw.

Conversely, ntshiab phenolic lipids ntawm ntau yam saw-ntev fatty acids tau npaj nrog ferulic acid [346]. Cov synthesis koom nrog bio-catalyzed kauj ruam (los ntawm Nosozyme) (Scheme 34).

Covkev ua haujlwm antioxidantKev tshawb nrhiav tau muab cov txiaj ntsig sib xyaw vim tias qhov kev ntsuam xyuas radical scavenging tsis pom muaj kev txhim kho nrog rau ferulic acid, thaum autoxidation ntawm linoleic acid nyob rau hauv lub micellar system pom ib co kev txhim kho, ntaus nqi mus ntxiv solubility.

Chemo-enzymatic synthesis ntawm phosphatidylcholines uas muaj phenolic acid thiab fatty acids tau tshaj tawm [347], nrog ib qho ntawm cov derivatives nquag, 1-(4-hydroxy-3,5-dimethoxy) cinnamoyl-2-acyl-sn-glycerol-3-phosphocholine, qhia txog kev ua haujlwm antioxidant zoo heev.

Ib txoj hauv kev sib txawv yog kom tau txais lipidic phenols los ntawm phenol thiab cov roj fatty acids dawb lossis cov esters sib xws, nrog rau cov lipase immobilized los ntawm Candida Antarctica ua biocatalyst [348]. Kev ua haujlwm antioxidant ntawm tyrosol tau nce thaum acylation, tab sis tsis muaj kev sib raug zoo nrog tus lej ntawm ob daim ntawv cog lus hauv pawg fatty acyl (Scheme 35).

Qee cov esters tau tsim los ntawm ntuj phenols thiab -lipoic acid nyob rau hauv cov tshuaj tiv thaiv catalyzed los ntawm Novozym 435 (lub immobilized lipase B los ntawm Candida Antarctica) nyob rau hauv ib tug butanone-hexane sib tov [349]. Kev ua haujlwm antioxidant tau txiav txim siab tsis yog los ntawm kev soj ntsuam radical scavenging nkaus xwb tab sis kuj los ntawm kev ntsuas qhov inhibition ntawm oxidation hauv tuna ntses roj emulsion. Cov ester 2-(3,4-dihydroxyphenyl)ethyl-5-(1,2-dithiolan-3-}}yl) pentanoate, tau los ntawm tyrosol thiab -lipoic acid, ua raws los ntawm aromatic hydroxylation (Scheme36), pom zoo heev antioxidant kev ua nyob rau hauv ob qho tib si kev ntsuam xyuas thiab, raws li cov kws sau ntawv, nws yuav siv tau raws li pro-tshuaj, vim hais tias, raws li hydrolysis, nws tso cov tebchaw uas tsis yog-tshuaj lom los yog txawm noj qab nyob zoo.

Tom qab ntawd, nws tau pom tias 2-S-lipoyl caffeic acid methyl ester yog ib qho inhibitor ntawm tyrosinase los ntawm tib neeg melanoma hlwb [350].

Lub hom phiaj los npaj ib qho lipidic phenol, kom tsis txhob muaj teeb meem sib cais ntawm cov sib tov sib xyaw, tau ua tiav los ntawm ntau lub tswv yim uas muaj cov tshuaj lom neeg thiab enzymatic catalysis. Immobilized lipase los ntawm Candida Antarctica (CAL-B) tau siv nyob rau hauv ib qho nruab nrab organic [351] (Scheme 37).

Tom qab tus cwj pwm, qhov npaj tau 1-[11-(ferulyloxy)undecanoyl)glycerol nyob rau hauv-mus tshuaj tua kab mob, antioxidant thiab cytotoxic kev tshawb fawb. Kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob yog nruab nrab, kev ua haujlwm antioxidant yog qhov zoo heev thiab kev ua haujlwm tiv thaiv qee cov kab mob qog noj ntshav tau cog lus tseg, yog li cov kws sau ntawv tau kwv yees cov kev siv tshuaj pleev ib ce thiab biomedical.

Transesterification cov tshuaj tiv thaiv siv Candida Antarctica lipase B tau ua, kho 4-hydroxyphenyl acetic acid nrog triolein thiab cov roj ntses, tau txais cov khoom siv hluavtaws uas muaj cov tshuaj tua kab mob antioxidant thiab cov kab mob [352].

5.2. Tshuaj Syntheses ntawm Lipidic Phenols

Lipidic phenols tau npaj ua esters, los ntawm phenols nrog ntev-chain carboxylic acids los yog los ntawm phenolic acids. Xaiv cov piv txwv ntawm hluavtaws lipidic phenols tau tshaj tawm hauv Table 1.

Anacardic acid, los ntawm cov txiv ntoo tshiab thiab qhuav ntawm Anacardium occidentale, tau hloov pauv mus rau hauv isobenzofuranones, raws li tau piav qhia hauv Scheme 38, nrog rau cawv (A) lossis keto (K) ua haujlwm nyob rau hauv cov saw ntev [360].

Ob leeg isobenzofuranones A thiab K, nrog rau acyclic precursor, tau nruab nrab mus rau qhov tseem ceeb hauv kev tshuaj ntsuam cytotoxicity nrog tib neeg kab mob qog noj ntshav.

Kev muaj peev xwm antioxidant zoo ua kom cov roj txiv roj ruaj khov tau pom nrog tsev neeg ntawm phenolic fatty acid esters, npaj los ntawm 3, 4-dihydroxy benzoyl cawv (protocatechuic cawv) lossis hydroxytyrosol thiab fatty acids. Cov tshuaj tiv thaiv tau ua nyob rau hauv anhydrous THF, nyob rau hauv lub xub ntiag ntawm ib tug carbodiimide thiab DMAP [361]. Txhua nees nkaum lub tebchaw tau tshawb xyuas raws li muaj peev xwm antioxidants hauv cov roj txiv roj refined. Qhov ntev ntawm alkyl saw txuas rau lub nplhaib phenyl zoo li cuam tshuam rau kev ua haujlwm.

Tom qab qhov kev tshawb pom tias 5-alkyl- thiab 5-alkylresorcinols, cais los ntawm cov nceb-chav Merulius incarnates, inhibited methicillin-resistant Staphylococcus aureus [362], ib txoj kev zoo hluavtaws yog tsim nyog, vim lawv tsis tau yooj yim. muaj, tab sis yog ib qho tseem ceeb rau kev soj ntsuam, metabolic, thiab bioactivity kev tshawb fawb. Ib txoj kev dav dav, raws li Wittig cov tshuaj tiv thaiv, tau tsim [363] los kov yeej qhov teeb meem ntawm alkyl saw qhia rau hauv lub nplhaib aromatic. Qhov teeb meem tau daws los ntawm kev ua haujlwm ntev-chain alkanols, thaum muaj, nrog ib nrab ruaj khov benzylphosphoniumyilids lossis, hloov pauv 3,5-dimethoxybenzenecarbaldehyde nrog alkyl phosphonium ylids. Cov txheej txheem xa tawm 5-alkylresorcinols nrog alkyl chains mus txog 25 C atoms. Cov tshuaj tiv thaiv tau ua nyob rau hauv dej los yog dej-DMSO sib tov, nrog MW irradiation, nyob rau hauv pressurized los yog nyob rau hauv ib tug qhib hlab ntsha. Ib qho piv txwv rau txhua txoj kev yog qhia hauv Scheme 39.

Nruab nrab mus rau qhov zoo hauv vitro antioxidant kev ua tau pom los ntawm 1,2-dibutanoyloxy-2-(4-hydroxy-3-}methoxyphenyl)ethyl butanoate, lipidic phenol tau los ntawm ferulic acid [354] .

2-Methyl-5-[(2Z)-non-2-en-1-yl]benzene-13-diol thiab 5-[(2Z)-non{ {10}}en-1-yl]benzene-1,2,3-triol tau npaj ua hluavtaws derivatives ntawm natural5-[(2Z)-non{18} }en-1-yl]benzene-1,3-diol (climacostol), tshuaj tiv thaiv hauv protozoan Climacostomum virens[355]. Kev hloov kho cov qauv hauv lub nplhaib uas muaj ntxhiab (ib qho methyl thiab hydroxylgroup, feem) ua rau muaj kev toxicity.

Long-chain alkyl hydroxycinnamates were prepared from the corresponding monoesters of malonic acid and benzaldehyde derivatives by Knoevenagel condensation [364]. The observed antioxidant activity followed the order caffeic esters > sinapic esters >ferulic esters muaj.

12-Hydroxy-9-octadecanoic acid (ricinoleic acid) tau hloov pauv hauv (Z)-methyl-12-aminooctadeca-9-enoate thiab tom qab ntawd cuam tshuam nrog phenolic acids, tsim cov amides sib xws [356 ]. Kev tshawb nrhiav tshuaj tiv thaiv antioxidant tau qhia tias kev hloov pauv ntawm phenolic acids nrog lipophilic moieties txhim kho lawv cov antioxidant thiab anticancer zog.

Nws tsim nyog taw qhia txog hom kev sib txawv ntawm lipidic phenols, uas yog phenyl sulfonyl furoxan derivatives ntawm caffeic thiab lwm yam phenolic acids [357]. Dhau li ntawm cov kev ua haujlwm zoo antioxidant hauv vivo, cov tebchaw no tau pom cov tshuaj tiv thaiv coagulant thiab vasodilatation teebmeem uas tau txais txiaj ntsig los ntawm NO-tso peev xwm.

Caffeic lossis 3,4-dimethylcaffeic acids tau hnov ​​​​mob nrog malic acid thiab tom qab ntawd ua ke nrog monoglycerides fatty acids nrog cov saw ntev li ntawm 8 txog 18 C atoms [359]. Kev sib xyaw ua ke ntawm phenolic thiab fatty acids tau muab cov 6 amphiphilic compounds uas tau sim rau kev ua haujlwm. Lawv tau ua pov thawj tias tsis muaj tshuaj lom thiab muab cov roj-hauv-dej emulsions ruaj khov, muaj peev xwm rau zaub mov, tshuaj, thiab kev lag luam tshuaj pleev ib ce, raws li cov kws sau ntawv.

6. Polyphenols

Ntujpolyphenolsua ib pawg neeg coob thiab faib ntau ntawm bioactive molecules hauv cov nroj tsuag noj tau, nrog rau bioactivities xws li kev tiv thaiv kab mob plawv mus rau kev tiv thaiv kab mob cancer [365-368].

Polyphenols yog tus cwj pwm los ntawm qhov muaj benzo-fused heteroaromatic nplhaib ntawm pyrene lossis Pyridium hom. Lawv feem ntau yog lub npe hu ua semi-systematic nomenclature, raws li niam txiv heterocycle. Yog li, benzopyrene derivatives nrog ib tug phenyl substituent yog hu ua flavones, thaum phenol hloov benzophenones yog qhia raws li flavones Cov qauv ntawm niam txiv sib txuas thiab lawv cov phenyl derivatives yog sau hauv daim duab 9.

Lub synthesis ntawm ntuj thiab semi-synthetic heev oxidized bioactivepolyphenolstau tshuaj xyuas xyoo 2008, sib tham txog kev nce qib thiab cov teeb meem [369]. Tsis tas li ntawd, kev tsim khoom tau zoo dua thiab ruaj khov tuaj yeem los ntawm cov chaw tsim khoom microbial cell, raws li kev tshuaj xyuas hauv 2018 [370].

Kev hloov tshuaj lom neeg ntawm ntuj phenols tuaj yeem ua rau cov tsiaj muaj txiaj ntsig zoo dua yog tias cov yam ntxwv ntawm cov khoom siv lom neeg nkag siab. Yog li, cov txiaj ntsig ntawm kev hloov kho tshuaj rau cov neeg sawv cev polyphenols tau tshaj tawm hauv qab no.

6.1.Phenols los ntawm Chroman

Catechin yog polyphenol ntawm tsev neeg flavanol uas tuaj yeem pom hauv cov tshuaj yej ntsuab. Cov txiaj ntsig tau tshaj tawm hauv daim duab 10 tau npaj los ntawm racemic catechin (tetra methoxy, pentaacetoxy, thiab cyclic) [371]. Catechin thiab cov derivatives tau sim rau cov tshuaj tiv thaiv kab mob tiv thaiv kab mob hauv paus-colonizing fungi, uas tau khaws cia, txawm tias muaj kev ua haujlwm qis dua, hauv cov tebchaw tsawg dua.

Lub antioxidative radical scavenging ntawm (ntxiv rau)-catechin, probed tiv thaiv galvinoxyl radical, yog txhim kho raws li cov tshuaj tiv thaiv nrog ninhydrin [374].

Txhawm rau daws qhov teeb meem ntawm kev ua kom tsis muaj zog ntawm cov kab mob, cov kev tshawb fawb tau tsom rau kev npaj thiab kuaj cov khoom siv hluavtaws ntawm catechin. Cov txheej txheem etherification ntawm 3-hydroxyl pawg nrog linear alkyl chains ntawm qhov ntev sib txawv los yog nrog cov pab pawg benzyl hloov pauv tau muab lub tsev qiv ntawv ntawm 3-O-alkyl analogs ntawm catechin [372] uas tau siv los kuaj cov tshuaj tiv thaiv kab mob. raws li kev ua haujlwm ntawm cov qauv. Cov khoom sib xyaw nrog cov saw ntev ntev (C14-C16) tau nthuav tawm cov haujlwm tsis muaj zog dua li cov sib txuas nrog C8-C12 chains.

Ntxiv mus, sib txawv ntawm -OH functionality nyob rau hauv 3, kaum ob derivatives ntawm (-)-catechin tau npaj [373]. Tsuas yog peb lub tebchaw pom muaj cov kab mob tua kab mob thiab tshuaj tua kab mob siab dua li cov tshuaj txheem (neomycin thiab miconazole). Cov kev tshawb fawb molecular docking pom zoo nrog cov txiaj ntsig kev sim.

Brazilin thiab oxidized analog brazilein (Daim duab 11) yog chromane derivatives pom nyob rau hauv cov nroj tsuag (Caesalpinia sappan L.), paub txog lawv cov khoom tiv thaiv. Novel hluavtaws derivatives tau npaj los tshawb txog lawv cov haujlwm antitumor. Lub synthesis ntawm Brazilians [375] tau ua tiav pib los ntawm 1, 3-dihydroxybenzene (resorcinol) thiab 3-chloropropanoic acid, nrog rau kev tsim ntawm qhov tseem ceeb nruab nrab 7-hydroxy-4-chromanone . Cov synthesized Brazilians (Daim duab 1l) tau sim rau cov tshuaj tiv thaiv kab mob tiv thaiv ntau tus tib neeg cov kab mob qog noj ntshav, tab sis tsuas yog qee qhov ntawm cov khoom siv hluavtaws tau pom qee qhov kev txhim kho nrog kev hwm rau cov tsis hloov pauv brazilein.

6.2. Phenols los ntawm Chromen

Coumarin (2H-chromen-2-ib qho), feem ntau derivative ntawm chromen, thiab hloov coumarins muaj nyob rau hauv cov nroj tsuag ntsuab, qhov uas lawv tawm tsam sib txawv [377].

Xav txog qhov muaj ntau yam ntawm cov tshuaj tiv thaiv ua rau coumarin heterocyclessystem [378, ntau cov coumarins hloov pauv tau raug tsim tawm thiab cov haujlwm muaj txiaj ntsig tau pom nrog coumarin-fused 14A-thiazepines, synthesized pib ntawm 4-hydroxycoumarins(Scheme 40)[379]

Coumarins thiab benzocoumarins hloov nrog ib pawg hydroxyl hauv 7- lossis 8- txoj haujlwm tau npaj thiab kuaj hauv vitro rau ntau yam kev ua ub no [380]. Feem ntau, lawv tau xa cov khoom muaj zog superoxide anion scavengers thiab inhibited hauv vitro lipid peroxidation; Ntawm qhov tod tes, lawv tsis pom qhov tseem ceeb lipoxygenase inhibitory kev ua haujlwm.

6.3.Phenols los ntawm Chromon

Quercetin (3,3'4',5,7-pentahydroxyflavone) yog flavonol muaj nyob hauv cov nroj tsuag, zaub mov, thiab dej haus, feem ntau ua ke nrog fisetin (3,3'4',7-tetrahydroxyflavone) .

Qhov kev txaus siab ntawm quercetin tau tshwm sim los ntawm nws cov tshuaj tiv thaiv kab mob, tiv thaiv kab mob, thiab antioxidant lub luag haujlwm. Qhov tseem ceeb tshwj xeeb yog muab los ntawm cov nyhuv anti-hypertensive [381]. Ntau cov khoom siv hluavtaws tau npaj nrog lub hom phiaj kom tau txais cov neeg sib tw tiv thaiv kabmob kheesxaws uas tuaj yeem kov yeej cov teebmeem quercetin: (i) solubility tsawg hauv dej, (ii) bioavailability tsawg, thiab (ii) ceev degradation. Kev tshawb fawb txog kev ua haujlwm lom neeg tsis txaus los ntsuas qhov ua tau zoo ntawm cov khoom siv, txawm hais tias qee qhov zoo li pheej hmoo [382]. Ntawm qhov tod tes, yooj yim complexation nrog Cu (I) muab ib tug Cu (quercetin) (bipy) complex nrog enhanced antioxidant zog piv rau dawb quercetin [383].

Qhov kev txaus siab ntawm cov khoom kho mob ntawm quercetin thiab derivatives tsis txwv rau cytotoxicity, raws li pom tau los ntawm tus naj npawb ntawm patents qhia ntawm 2010 thiab 2015 [384]. Xaiv cov piv txwv muaj txiaj ntsig raug sau hauv Table 2.

Feem ntau ntawm cov derivatives no koom nrog kev hloov pauv ntawm txhua pawg hydroxyl, nrog rau kev hloov kho ntawm pawg C-3-hydroxyl uas ua rau muaj kev txhim kho ntawm kev tiv thaiv kab mob. Tsis tas li ntawd, bioactivity tau nce ntxiv los ntawm nanotechnology.

Qhov teeb meem ntawm scarce solubility nyob rau hauv dej ntawmflavonoidspolyphenols tau hais los txiav txim siab derivatives nrog hydrophilic substituents, xws li sulfate [385].

Ib txoj hauv kev sib txawv yog los npaj conjugates suab thaj nrog flavonoid ua aglycone. Glucose, galactose, thiab rhamnose tau siv, inter alia.

Enzymatic synthesis tau ua tiav hauv kev hloov kho cov khoom sib txuas uas tsis yog tsuas yog soluble xwb tab sis kuj muaj ntau hom tshuaj hauv tshuaj [386] lossis cosmeceutical [387] daim ntawv thov.

Nws yog qhov nthuav tias rutin (2-(3,4-dihydroxyphenyl)-5,7-dihydroxy-3-[ -L-rhamnopyranosyl-(1→6){ {11}}D-glucopyranosyloxy]-4H-chromen-4-ib qho) tau hloov pauv ntxiv los ntawm cov tshuaj tiv thaiv enzymatic transesterification rau hauv mono- thiab di-acetate derivatives (Scheme 41) nrog cov khoom tiv thaiv oxidant thiab ntau dua muaj peev xwm nkag mus rau hauv cell membrane ntawm murine macrophages [388]. Tsis tas li ntawd, acetoxy-hloov rutins tsis muaj tshuaj lom rau cov qe menyuam thiab cov enzyme tuaj yeem rov qab siv dua.

Qhov tseem ceeb ntawm cov piam thaj hloov flavonoids yog ua piv txwv los ntawm myricitrin (myricetin-3-O- -L-rhamnopyranoside), uas nws cov tshuaj tiv thaiv oxidant muaj kev tiv thaiv DNA puas tsuaj [389].

Ib qho tshiab flavonoid scaffold tau npaj los qhia salicylate thiab trimethoxybenzene pawg hauv flavonoids [390]. Tag nrho cov tebchaw tau raug soj ntsuam rau kev ua haujlwm tiv thaiv kab mob tiv thaiv peb tus tib neeg cov qog hlwb uas qhia txog kev ua haujlwm zoo.

6.4.Phenols los ntawm 2, 3-dihydrochromon

Ntawm cov flavanones, cov metabolites theem nrab ntawm cov nroj tsuag nrog ib tug broad spectrum ntawm biological kev ua ub no, pinstriping (5-hydroxy-7- methoxy-flavanone) tau txais kev txaus siab vim hais tias nws yog ib feem tseem ceeb nyob rau hauv lub rhizome ntawm fingerroot (Kaempferia pandurata), siv nyob rau hauv cov teb chaws Es Xias ua noj ua haus, paub tias muaj ntau yam pharmacological kev ua ub no, uas cov tshuaj tiv thaiv kab mob yog cog lus.

Allylation thiab prenylation ntawm pinostrobin tau ua tiav siv MW irradiation (Mitsunobu thiab metathesis cov tshuaj tiv thaiv, Claisen thiab Cope rearrangements) (Scheme 42), muab cov tebchaw uas tau sim tawm tsam ntau cov kab mob qog noj ntshav [391]. Cov derivatives tau muaj zog ntau dua li pinostrobin, qhov tshwm sim uas cov kws sau ntawv tau hais tias muaj kev cuam tshuam zoo dua nrog cov hom phiaj lom neeg, vim qhov nce lipophilicity muab los ntawm alkenyl substituents.

Pinostribin yog prenylated nyob rau hauv tej yam yooj yim SN2 tej yam kev mob (Scheme 43), muab ib tug sib tov ntawm cov khoom, feem ntau ntawm cov uas poob lub flavanone qauv. Lawv tau raug muab cais thiab sim tshuaj tua kab mob [392], uas qhia tau hais tias muaj txiaj ntsig zoo. Interestingly, ob peb prenylated coumarins thiab quercetin raug cais tawm ntawm cov cag ntoo ntawm Broussonefia papyrifera ua metabolites nrog, qee zaum, kev ua haujlwm cytotoxic [393].

Astilbin, qab zib derivative ntawm flavanol taxifolin, yog muab rho tawm los ntawm cov nroj tsuag tshuaj ntsuab, feem ntau siv hauv cov tshuaj suav tshuaj. Txawm li cas los xij, rau lawv txoj kev siv tshuaj, astilbin muaj los ntawm kev rho tawm tsis txaus. Cov txheej txheem ua tau zoo kom tau txais astilbin los ntawm taxifolin tso siab rau microbial fermentation nyob rau hauv genetically-engineered Escherichia coli (Scheme 44) [394].

Ib lub tshuab biocatalytic cascade tau tsim los npaj 4'-O-glucoside derivatives ntawm naringenin (5,7-dihydroxy flavanone), flavonoid nrog ntau cov teebmeem bioactive, pom hauv txiv hmab txiv ntoo thiab txiv kab ntxwv [395]. Txoj kev cia siab rau kev tsim cov tshuaj uridine diphosphate los ntawm sucrose thiab rov siv nws, ua tiav kev npaj ua kom tiav. Los ntawm tib txoj kev, quercetin 7-OaL-rhamnoside tau txais.

Interestingly, myricitrin (myricetin{0}}O- -L-rhamnopyranoside)[389] thiab naringenin, tam sim no nyob rau hauv rho tawm ntawm Cynara cardunculus, ib tug haib tshuaj tua kab mob, nthuav tawm phytotoxic cuam tshuam rau nplooj ntawm Trifolium incarnatum, qhib lub txoj kev mus rau tej yam ntuj tso tshuaj tua kab mob, ib thaj teb tseem ceeb zuj zus vim muaj kev tiv thaiv ntawm cov nroj tsuag uas nquag siv[396].

7. Curcumin thiab Curcuminoids

Curcumin, [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dionel, a daj xim cais los ntawm turmeric (Curcuma longa Linn), yog ib qho kev sib xyaw ua ke uas, tsawg kawg los ntawm kev nyeem cov ntaub ntawv ntawm nees nkaum xyoo dhau los, zoo li ib hom panacea rau tag nrho cov kab mob niaj hnub no, mob qog noj ntshav thiab Alzheimer's kab mob suav nrog. Phenolic-OH pawg kom ntseeg tau cov khoom tiv thaiv oxidant, qhov uas nws kim heev conjugation vim ketoenol equilibrium (Scheme 45) yog lub hauv paus ntawm photodynamic kev ua.

Ob peb qhov kev tshuaj xyuas tsis ntev los no tham txog cov yam ntxwv ntawm kev ua haujlwm lom neeg [397-400] thiab daim ntawv thov kev kho mob tau [70,292,401-404] ntawm curcumins thiab derivatives. Qhov tseem ceeb, xws li kev xa khoom tshiab thiab kev sib koom ua ke nrog lwm cov tebchaw, kuj tau tham txog, nrog rau cov txheej txheem ntawm kev ua [405]. Kev txaus siab ntxiv yog mob siab rau cov tshuaj curcumin-based tiv thaiv kab mob neurodegenerative [406], tshwj xeeb tshaj yog Alzheimer's [407] thiab mob qog noj ntshav [408].

Qhov kev tshawb nrhiav tshiab curcumin derivatives yog mob siab rau los ntawm (i) qhov tsim nyog ntawm kev nce cov khoom muaj, thiab (i) qhov tsim nyog ntawm meliorating cov solubility nyob rau hauv ib tug aqueous tov.

Qhov tseem ceeb, tsuas yog kho curcumin nrog Cu (II), Cu (curcumin) (bipy) complex raug cais tawm thiab nws yog ib qho zoo dua antioxidant thiab DNA khi piv rau curcumin dawb thaum tsis muaj tshuaj lom, raws li nws cov khoom siv tshuaj tua kab mob [383] . Nws kuj tau tshaj tawm tias silver-curcumin nanoconjugates, npaj los ntawm ib txoj kev sonochemical, tau sim ntawm cov kab mob ntawm daim tawv nqaij thiab rau cov kab mob tua kab mob tiv thaiv Escherichia coli. Cov txiaj ntsig tau qhia tias cov nyiaj nanoparticles tau ua biocompatible los ntawm curcumin, thaum lawv ua curcumin ntau photostable thiab muaj zog dua li cov tshuaj tua kab mob [409].

Peb tham txog curcumin derivatives raws li cov qauv kev hloov pauv.

7.1. Cov kev hloov me me

Cov qauv me me hloov pauv tuaj yeem hloov qhov ua tau zoo ntawmcurcuminbioactivity. Piv txwv li, qhia txog ib pawg methyl nyob rau hauv txoj hauj lwm 2 lossis ob pawg methyl, xws li hauv 2, 7-dimethylcurcumin, txhim kho kev tiv thaiv angiogenesis thiab tiv thaiv qog loj hlob [410] tau pom, nrog rau kev ua kom muaj zog tiv thaiv kab mob[411] ] thiab stability tiv thaiv enzymatic txo [412], nrog rau kev hwm ntawm curcumin.

Diacetylcurcumin, yooj yim npaj los ntawm acetylation ntawm niam txiv compound, qhia tau hais tias zoo heev antibacterial kev ua si [413] thiab nws yog zoo nyob rau hauv antiarthritic kev ua si nyob rau hauv nas (Table 3) [414].

Cov tshuaj tiv thaiv oxidant ntawm curcumin tau muab piv nrog cov dimethoxy metabolites thiab hydrogenated derivatives [415]. Cov txiaj ntsig tau qhia tias cov saturated derivatives (tetrahydro-, hexahydro- thiab octahedron-coumarins) tau nce kev ua haujlwm antioxidant nrog rau coumarin (Table 3).

Cov derivative tau los ntawm kev qhia txog cov khoom siv prenyl hauv ob lub nplhaib uas muaj ntxhiab tau sim tawm tsam oxidative kev nyuaj siab [416](Table 3), uas qhia qhov sib npaug lossis zoo dua antioxidant zog nrog rau curcumin.

Kev hloov pauv hnyav dua tau ua, qhia cov khoom siv hluav taws xob rho tawm mus rau hauv benzene rings, lossis txawm tias condensing heterocycles (Table 3) [417].

7.2. Hloov pauv hauv UIinsaturated Chain

Feem ntau cov khoom siv hluavtaws los ntawm kev qhia txog cov khoom hloov pauv hauv txoj haujlwm 4, yog li cuam tshuam rau curcumin tautomeric equilibrium.Ib qho tseem ceeb bioactivity txuas rau keto-enol equilibrium yog kev cuam tshuam nrog amyloid (A) aggregation, tam sim no nyob rau hauv Alzheimer's kab mob. Kev tshawb nrhiav dav dav ntawm keto-enol tautomeric equilibria hauv kev hloov pauv curcumins tau ua [432-434]. Tsis ntev los no, nws tau tshaj tawm tias 4,4-disubstituted curcumin (Daim duab 12), qhov twg daim ntawv keto tsuas yog ib qho ua tau, khi non-fibrillar soluble A oligomers, dhau los, raws li cov kws sau ntawv hais, "ib tiam thawj zaug. compound aiming A oligomers [435].

Fluorinated curcumin derivatives pom qhov tseem ceeb inhibition ntawm thioredoxin-interacting protein (TXNIP), uas yog txuam nrog ntau yam kab mob [418].

Ib tug xov tooj ntawm curcumin derivatives hloov los ntawm acid los yog ester pawg nyob rau hauv position4 tau npaj [436](Daim duab 13). Acidity, lipophilicity, thiab kinetic stability tau txiav txim siab, ua ke nrog dawb radical scavenging kev ua si, txhawm rau ntsuas kev sib raug zoo ntawm cov qauv thiab kev ua haujlwm. Cov ester derivatives nthuav tawm kev xaiv tiv thaiv kab mob qog noj ntshav, tej zaum yog vim lawv cov lipophilicity ntau dua ua tsaug rau curcumin.

Ib txoj hauv kev sib txawv yog kev qhia txog qhov tsis txaus ntseeg nyob hauv txoj hauj lwm 4 (Table 3), los ntawm Knovenagel cov tshuaj tiv thaiv nrog benzenecarbaldehyde, 4-hydroxybenzaldehyde, thiab 4-hydroxy-3-methoxy-benzaldehyde (vanillin) 419 ]. Cov derivatives tau txais tau raug sim rau kev tiv thaiv kab mob npaws tawm tsam P. falciparum, thiab vanillin derivative yog qhov muaj zog heev.4-Benzylidene curcumins, npaj los ntawm 2-hydroxybenzenecarbaldehyde [420] thiab 4-benzylidenecurcumins, yog tshawb xyuas raws li cov tshuaj tiv thaiv oxidant thiab ob qho tib si tau zoo hauv kev txo cov kab mob cataract hauv kab lis kev cai nas lo ntsiab muag.

7.3. Kev hloov kho ntawm -dicarbonyl Moiety

Kaum yim derivatives tshiab, tseem muaj cov hepta-1, 6-dien-3, 5-dione qauv ntawm curcumin, tab sis nrog ib qho ntawm cov pab pawg carbonyl koom ua ke rau hauv cycloheptanone moiety, tau synthesized los ntawm ntau yam hluavtaws zoo [421]. Ib qho piv txwv ntawm kev hloov tropinone tau tshaj tawm hauv Table 3. Cov kws sau ntawv tau ntseeg siab tias tsev neeg ntawm dicarbonyl curcumins nrog lub nplhaib tropane yuav muaj kev ua haujlwm tseem ceeb txij li cov monocarbonyltropanone yooj yim yog cytotoxic rau cov qog nqaij hlav cancer mis.

Ib lub tsev qiv ntawv ntawm curcumin derivatives tau txais thaum cov tshuaj tiv thaiv nrog ib lossis ob qhov sib npaug ntawm sulfonamides (xaiv cov tshuaj sulfa) (Scheme 46) [437]. Antibacterial thiab antifungal kev ua ub no tau soj ntsuam tawm tsam Gram-positive thiab Gram-negative microorganisms, nrog cov txiaj ntsig zoo.

3,4-Dihydropyrimidin-2(1H)-ib qho thiab thione analogs ntawm curcumin (Table 3) tau raug tsim los ntawm cov txiaj ntsig zoo los ntawm ib lub lauj kaub ntau lub ntsiab lus cyclo condensation nyob rau hauv MW irradiation [425]. Antibacterial thiab antioxidant kev tshawb fawb tau ua nyob rau hauv vitro nrog cov txiaj ntsig tau txiav txim siab los ntawm cov kws sau ntawv "nruab nrab" hauv cov ntaub ntawv qub thiab "zoo heev" tom kawg.

Ib qho pyrazole derivative ntawm curcumin tau npaj los sim ua ke rau hauv tib lub molecule cov yam ntxwv ntawm curcumin thiab asteroid-zoo li compound (cyclohexyl bisphenol A) [422]. Lub compound tau pom tias yog neuroprotective nyob rau hauv cell kab lis kev cai soj ntsuam, kuj tiv thaiv intracellular thiab extracellular amyloid. Tsis tas li ntawd, nws tau pom tias muaj kev nco-txhim kho cov khoom hauv kev kuaj nas khoom paub [423].

7.4 ib. Ib feem hloov ntawm -dicarbonyl Moiety

Ib nrab hloov ntawm -dicarbonyl moiety ntawm curcumin tau suav hais tias muaj txiaj ntsig los daws qhov teeb meem ntawm nws qhov tsis txaus ntseeg. Ib tug series ntawm mono-carbonyl analogs ntawm curcumin, synthesized los ntawm opportunely hloov benzaldehyde thiab ib tug cycloalkane [438-440]. Kev ruaj ntseg ntawm kev hloov pauv cyclopentanones thiab cyclohexanones tau txhim kho hauv vitro. Cov kev ua cytotoxic kuj tseem siab dua nrog cyclohexanones, nrog rau qhov tseem ceeb ntawm cov khoom siv hluav taws xob hloov pauv (Scheme 47).

Cov aminocarbonyl curcumin analogs tau sim tawm tsam pro-inflammatory cytokines, nthuav tawm lub peev xwm inhibitory ntau dua li curcumin.

Symmetrical bis (arylidene) ketones tau npaj los ntawm reacting cycloalkanones nrog hloov benzaldehydes, nyob rau hauv ib tug acid-catalyzed aldolic condensation. Feem ntau ntawm cov synthesized compounds pom inhibition ntawm zes qe menyuam qog noj ntshav cell loj hlob, txawm tias cov hlwb resistant rau cisplatin [441].

Ob peb hluavtaws aminocarbonyl curcumin analogs tau sim tawm tsam Trichomonas vaginalis (xws li "feem ntau tsis muaj kab mob sib kis ntawm kev sib deev hauv ntiaj teb")[442];15-diphenylpenta-1,4-diene{ {5}}ib,15-bis(2-chlorophenyl)Penta-1.4-diene-3-ib thiab 2,6-bis({ {13}}chlorobenzylidene)cyclohexanone nthuav tawm cov haujlwm tseem ceeb ntawm cov tshuaj tiv thaiv kab mob ntawm qhov muaj txiaj ntsig zoo qis dua li curcumin.

Tsis ntev los no, thawj zaug, tab sis tau txais txiaj ntsig zoo heev, cov txiaj ntsig tau txais nrog (2E,6E)-2,6-bis(2(trifluoromethyl)benzylidene)cyclohexanone, uas tau pom los kho cov mob ntshav qab zib hauv nas [426] (Table 3).

Ib lub kaum os curcumin aminocarbonyl analogs tau ua ke, txhawm rau nrhiav cov tebchaw uas muaj tshuaj lom neeg ruaj khov thiab, thaum kawg, kev ua haujlwm zoo dua los tiv thaiv qog noj ntshav tawm tsam qee cov qog nqaij hlav hauv tib neeg [427]. Ob ntawm lawv (Table 3) ua tau raws li qhov yuav tsum tau ua thiab tau ua tiav kev sim tshuaj tiv thaiv kab mob melanoma, uas ua rau muaj tshuaj lom 428].

Cov curcuminoids tshiab suav nrog 4H-pyran heterocycles tau npaj los ntawm ib lub lauj kaub condensation ntawm curcumin nrog propanodinitrile thiab hloov benzenecarbaldehyde (Scheme 48) [443]. Qhov kev hloov pauv ntawm -dicarbonyl moiety txhim kho inhibition ntawm -glucosidase, ib qho ntawm cov enzymes lub luag haujlwm rau carbohydrate hydrolyses thiab yog li ntawd rau postprandial hyperglycemia. Cov yam ntxwv no, ua ke nrog kev ua haujlwm antioxidant, muaj txiaj ntsig zoo tiv thaiv kab mob ntshav qab zib mellitus, tshwj xeeb tshaj yog vim tias tsis muaj tshuaj lom neeg tau pom zoo rau tib neeg txoj hnyuv microflora.

7.5. Txo qhov ntev ntawm Unsaturated Chain

Curcumin analogue, 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)Penta-2,4- diene-1-ib qho pom muaj kev tiv thaiv kab mob hauv cov nas (Table3)[429]. Zoo sib xws com-pounds nrog tib lub cev pob txha tau siv los tsim qhov tseem ceeb ntawm cov pa oxygen reactive hom upregulation hauv kev tawm tsam ntawm qog nqaij hlav [444]. Raws li cov kws sau ntawv, cov tshuaj no tau cog lus rau kev txhim kho cov tshuaj tiv thaiv kab mob qog noj ntshav nrog ob peb yam kev mob tshwm sim.

Ib qho zoo sib xws tab sis luv dua, (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenyl prop-2-ene-1-ib, tau npaj pib los ntawm 2-hydroxyphenyl methyl ketone thiab benzoyl

chloride (Tshooj 49). Cov txiaj ntsig molecule tau pom kev xaiv cytotoxicity ntawm lub mis mob qog noj ntshav MCF-7 hlwb [445], tib neeg cov kab mob qog noj ntshav hauv tib neeg [446] thiab tib neeg osteosarcoma hlwb[447].

7.6. Derioatioes tsuas yog "Ib nrab" ntawm Curcumin Structure

Ib tsev neeg ntawm cov tebchaw, muaj npe los ntawm cov kws sau ntawv retro-curcuminoids, tau npaj los tswj tsuas yog "ib nrab" ntawm cov qauv curcumin (Scheme 50), vim tias -dicarbonyl moiety tau suav tias yog lub luag haujlwm rau curcumin scarce stability [448]. Cov txiaj ntsig tau tshwm sim tau qhia txog kev ua haujlwm cytotoxic tawm tsam tib neeg cov kab mob qog noj ntshav, tab sis lawv tsis ua rau cov hlwb noj qab haus huv.

Ib qho hluavtaws amide analog tau pom cov tshuaj tiv thaiv oxidative thiab tiv thaiv kev mob. Nws tau sim nrog cov txiaj ntsig zoo ntawm cov kab mob hepatic steatosis hauv cov nas uas muaj kev rog rog [430](Table 3).

Ib lub tsev qiv ntawv ntawm curcumin-resveratrol hybrids tau tsim los ntawm hydrazide derivative ntawm hloov cinnamic acid thiab ib tug series ntawm hloov benzaldehydes [449]. Qhov piv txwv qhia hauv Scheme 51 yog hais txog qhov kev cog lus zoo tshaj plaws uas yog tus neeg sawv cev antitumor ntau lub hom phiaj.

7.7. Photosensitizers

Curcumin tej zaum yuav yog ib qho zoo heev photosensitizer, vim nws cov biocompatibility zoo, tab sis kev siv tswv yim yog txwv tsis pub los ntawm nws qhov tsis tshua muaj kev ruaj ntseg thiab tsis tshua muaj solubility hauv dej. Ib qho kev daws teeb meem tau tshawb nrhiav npaj curcumin derivatives nrog cationic hloov pauv [450](Daim duab 14).

Tag nrho cov derivatives pom muaj kev ruaj ntseg nrog pH thiab kub. Raws li cov khoom siv photodynamic, lawv muaj peev xwm txhawb nqa photodynamic inactivation ntawm E.coli, nrog rau hom Hexa-cationic yog qhov zoo tshaj plaws, tej zaum yog vim muaj hydrophilicity siab.

Ib txoj kev tshawb fawb sib piv tau ua tiav ntawm cov curcumin derivatives sib xyaw ua ke ad hoc, nrog rau lub hom phiaj los ua kom cov ntaub so ntswg nkag mus, ua kom qhov nqus tau siab tshaj plaws. Yog li,1,11-diphenyl-1,3,8,10-undecatetraene-57-dione thiab 1,7-bis(4'-dimethylaminophenyl){{11 }},6-heptadienyl-3,5-dione tau nthuav tawm cov yam ntxwv zoo ntawm kev tsim cov pa oxygen reactive thiab, yog li ntawd, ntawm kev ua tau zoo hauv kev kho mob photodynamic [431]. 8. Cov lus xaus

Ntuj phenols thiab lawv cov derivatives nrog cov kev ua ub no ua ib lub ntsiab lus tshawb fawb loj hlob sai, vim lawv muaj ntau yam khoom siv tam sim no thiab yav tom ntej. Lawv cov qauv kev sib txawv muaj ntau txoj hauv kev ntawm kev hloov tshuaj lom neeg, tsom rau kev kov yeej cov teeb meem ntawm ntuj phenols. Txawm li cas los xij, sib nrug los ntawm qee cov lus qhia uas tau tshwm sim los ntawm ntau qhov kev tshaj tawm, xws li kev xav tau meliorate stability thiab bioavailability ntawm bioactive compounds, daim duab ntawm cov qauv kev cai tseem tsis tau tiav, nyob rau hauv view ntawm optimizing nyob rau hauv vivo thiab nyob rau hauv daim ntawv thov. .