Part 1: Anticancer Activity Of Natural And Synthetic Chalcones

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

Abstract: Mob qog noj ntshavyog ib yam mob tshwm sim los ntawm ntau yam txheej txheem (genetic, tiv thaiv kab mob, oxidation, thiab inflammatory).Anticancer kho moblub hom phiaj los rhuav tshem lossis nres kev loj hlob ntawm cov qog nqaij hlav cancer. Kev tiv thaiv kev kho mob yog qhov ua rau tsis muaj txiaj ntsig ntawm cov txheej txheem kho tam sim no. Cov phiaj xwm kev kho mob yog qhov ua tau zoo tshaj plaws vim muaj cov kev mob tshwm sim tsawg thiab tsis muaj zog. Ntawm cov me me molecule ntuj tebchaw, flavonoids tshwj xeeb tshaj yog txaus siab rau kev txheeb xyuas cov tshuaj tiv thaiv kab mob tshiab. Chalcones yog precursors rau tag nrho cov flavonoids thiab muaj ntau yam kev ua ub no lom. Kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob ntawm chalcones yog vim muaj peev xwm ntawm cov tshuaj no ua rau ntau lub hom phiaj. Ntuj chalcones, xws li licochalcones, xanthohumol (XN), pandurate (PA), thiab loncocarpine, tau kawm thiab hloov kho. Kev hloov kho ntawm cov qauv ntawm cov chalcones thiaj li yuav tau txais cov khoom sib txuas nrog cov khoom zoo tshaj plaws cytotoxic tau ua los ntawm kev hloov cov ntxhiab tsw qab, hloov cov ntxhiab tsw qab nrog heterocycles, thiab tau txais hybrid molecules. Ntau tus lej ntawm chalcone derivatives nrog cov seem xws li diaryl ether, sulfonamide, thiab amine tau txais, lawv qhov muaj txiaj ntsig zoo rau kev tiv thaiv kab mob. Kev hloov kho ntawm pawg amino hauv cov qauv ntawm cov amino chalcones yog ib txwm zoo rauantitumorkev ua si. Qhov no yog vim li cas hybrid molecules ntawm chalcones nrog sib txawv nitrogen heterocycles nyob rau hauv lub molecule tau txais. Los ntawm cov no, azoles (imidazole, oxazoles, tetrazoles, thiazoles, 1,2,3-triazoles, thiab 1,2,{5}}triazoles) yog qhov tseem ceeb tshwj xeeb rau kev txheeb xyuas cov tshuaj tiv thaiv kab mob tshiab.

Ntsiab lus: chalcone; azole; mob qog noj ntshav; bioactivity; kev sib cuam tshuam ntawm ligand-receptor

Nyem kom paub ntxiv cov khoom cuam tshuam

1. Taw qhia

Mob qog noj ntshavyog ib qho teeb meem tseem ceeb ntawm kev noj qab haus huv rau pej xeem uas muaj tsawg tsawg ntawm cov kev kho mob zoo, kev ua tsis zoo, thiab kev tuag siab [1]. Ntau cov qog nqaij hlav qog noj ntshav hloov metabolically rau cov nyhuv Warburg, uas suav nrog nce qabzib thiab kev nqus cov as-ham thiab lactic acid ntau lawm, txawm tias nyob rau hauv cov xwm txheej aerobic. [2] Kev paub tseeb ntawm kev kis mob qog noj ntshav muab cov ntaub ntawv tseem ceeb hais txog qhov ua tau thiab qhov tshwm sim ntawm cov pej xeem rau tus kab mob no, ua kom muaj kev cuam tshuam zoo los txheeb xyuas txoj hauv kev zoo ntawm kev tiv thaiv, saib xyuas, thiab kuaj mob. [3] Lub etiology ntawm cov qog nqaij hlav yog cuam tshuam los ntawm kev hloov pauv thiab ib puag ncig. Piv txwv li, cov ntaub ntawv hloov pauv caj ces tau pom hauv cov qog nqaij hlav cancer |4]. Vim li no, ntau cov kev tshawb fawb tau pom cov kev hloov genomic hauv kev mob qog noj ntshav los ntawm oncogenic cell-forming signaling pathways mus rau lub spectrum ntawm kev hloov nyob rau hauv txawv cancer subtypes [5]. Tsis tas li ntawd, nyob rau hauv cov txheej txheem oncogenic, inflammatory thiab kev tiv thaiv kab mob yog correlated nrog ntau cellular thiab humoral Cheebtsam thiab muaj ib qho kev taw qhia txoj kev. Nyob rau hauv cov ntaub ntawv ntawm o txuam nrog cov kab mob qog, cov txheej txheem yog ntev thiab hnyav. [6] Kev mob qog noj ntshav thiab mob qog noj ntshav tau paub tias muaj kev cuam tshuam hauv ob txoj hauv kev: txoj hauv kev hauv nruab nrab thiab txoj hauv kev tawm sab nraud. Txoj kev extrinsic yog qhib los ntawm kev pib ntawm oncological txheej txheem los ntawmmob. Nyob rau hauv cov ntaub ntawv ntawm txoj kev intrinsic, somatic deficiencies thiab genetic mutations activates signaling pathways thiab ua rau ib tug nce nyob rau hauv lub inflammatory teb [7]. Lwm qhov kev txiav txim siab ntawm mob qog noj ntshav yog kev ua kom lub cev tiv thaiv kab mob, uas cuam tshuam nrog ntau txoj hauv kev metabolic hauv cov qog nqaij hlav cancer [8]. Hauv cov neeg mob qog noj ntshav, ntau lub hlwb raug tso tawm mus rau hauv kev ncig txhua hnub. Rau kev tsim cov metastases, cov qog nqaij hlav cancer tawm ntawm qhov chaw tseem ceeb, nkag mus rau hauv cov hlab ntsha, raug rau cov hlab ntsha siab, hloov mus rau theem nrab cellular ib puag ncig, thiab cuam tshuam nrog lub cev tiv thaiv kab mob 9]. Kev loj hlob ntawm cov qog nqaij hlav cancer kuj yog tshwm sim los ntawm kev sib sau ntawm cov pa oxygen, uas muaj peev xwm ua kom cov macromolecules cuam tshuam thiab ua rau cov cell tuag [10]. Reactive oxygen thiab nitrogen hom (ROS / RNS) yog tsim los ntawm inflammatory cells thiab epithelial hlwb. ROS/RNS ua rau DNA denaturation nyob rau hauv lub cev nyob rau hauv lub siab ntawm cov txheej txheem inflammatory thiab ua rau pib ntawm carcinogenesis. DNA kev puas tsuaj, tshwj xeeb tshaj yog rau 8-oxo-7, 8-dihydro-2'-deoxyguanosine thiab 8-nitroguanidine, tau pom tias yog ib txoj hauv kev rau kev mob qog noj ntshav[ 11]. Cell apoptosis lossis programmed cell tuag yog ib txoj hauv kev tseem ceeb rau kev tswj cov kab mob carcinogenesis thiab yog kev cog lus ntawm cov cell, uas ua rau DNA tawg thiab chromatin condensation [12,13]. Muaj ob txoj hauv kev tseem ceeb apoptotic (kev tuag ntawm receptor thiab mitochondrial txoj kev). Ntau qhov kev tshawb fawb tau txheeb xyuas ntau lub hom phiaj rau kev kho mob qog noj ntshav [14]. Ua raws li cov hom phiaj no yog txhawm rau rhuav tshem lossis nres kev loj hlob ntawm cov qog nqaij hlav cancer [15]. Caspases, ib pawg ntawm cysteine ​​proteases uas degrade cellular proteins, yog lub hom phiaj tseem ceeb rau kev kho mob qog noj ntshav vim tias lawv ua lub luag haujlwm tseem ceeb hauv kev taw qhia apoptotic [16]. Txoj kev PI3K / AKT tseem suav hais tias yog ib qho ntawm cov txheej txheem tseem ceeb hauv kev tsiv teb tsaws ntawm tes, ntxeem tau, thiab kev hloov pauv los ntawm pulmonary mesenchymal epithelium. Tsis tas li ntawd, txoj kev taw qhia no cuam tshuam nrog kev loj hlob thiab metastases hauv lub raum cell carcinomas, apoptosis ntawm cov hlwb hauv pharyngeal carcinomas, thiab cuam tshuam rau kev loj hlob ntawm cov qog nqaij hlav cancer hauv kab noj hniav [17].

Lub hom phiaj tseem ceeb ntawm kev kho mob qog noj ntshav yog ua rau cov qog nqaij hlav cancer tsis muaj kev cuam tshuam rau cov qog nqaij hlav hauv lub cev lossis cov qog microenvironment [18]. Cov qog nqaij hlav cancer tsim los ntawm cov hlwb ib txwm yog qhov nyuaj rau kev kho mob nrog cov tshuaj kws khomob cov neeg ua haujlwm xaiv. Cov neeg ua haujlwm no ua los ntawm ntau lub tswv yim, xws li thaiv lub voj voog ntawm tes ntawm ntau theem, inducing apoptosis thiab tiv thaiv kev loj hlob ntawm cov qog nqaij hlav cancer, thiab cuam tshuam nrog metabolic reprogramming [19]. Ob qho tshuaj khomob thiab kev kho mob hluav taws xob ua rau muaj kev cuam tshuam DNA thiab ua rau lub voj voog ntawm tes lossis cell tuag. Txawm li cas los xij, lub cim tshiab ntawm kev kho mob qog noj ntshav yog ua raws li kev ua kom cov qog nqaij hlav hauv nruab nrog cev los ntawm kev koom nrog cov neeg ua haujlwm nrog cov txheej txheem tshwj xeeb ntawm kev ua lossis uas muaj txoj hauv kev paub txog kev txhim kho kev tiv thaiv [20].

Cov tshuaj cytotoxic raug cais tawm, raws li lawv cov txheej txheem ntawm kev ua, rau hauv cov tshuaj alkylating, cov hlau hnyav (platinum), cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob cytotoxic, thiab cell cycle blockers. Feem ntau cov cytotoxic compounds ua rau kev ncaj ncees ntawm DNA thiab cell faib hauv cov qog nqaij hlav cancer [21]. Kev kho mob siv cov platinum complexes raws li ib tug adjunct nyob rau hauvkev kho mob qog noj ntshavyog raws li lawv lub peev xwm ua rau qog cell tuag, raws li cov tebchaw muaj ntau yam kev ua ub no |22]. Cov laj thawj rau qhov tsis muaj txiaj ntsig ntawm kev kho mob qog noj ntshav yog metastases, rov tshwm sim, heterogeneity, tsis kam mus rau kws khomob thiab hluav taws xob, thiab txo qis lub cev tiv thaiv kab mob. Tag nrho cov kev kho tsis ua haujlwm no tuaj yeem piav qhia los ntawm cov yam ntxwv ntawm cov kab mob qog noj ntshav [23-25]. Mesenchymal qia hlwb yog ib hom cell feem ntau siv nyob rau hauv cov tshuaj regenerative. Cov hlwb no paub tias ua rau muaj kev cuam tshuam rau cov qog nqaij hlav cancer [26]. Kev tiv thaiv kev kho mob txuas ntxiv yog qhov tseem ceeb txwv kev kho mob rau cov neeg mob qog noj ntshav. Cov kev kho mob tam sim no (kev phais, kws khomob, thiab kev siv hluav taws xob) tsis muaj peev xwm vim muaj kev phom sij thiab tshuaj lom, tus neeg mob intolerance, thiab qhov muaj sia nyob mus ntev [27-30]. Kev kho mob phais thiab kev kho hluav taws xob tsom txhawm rau tshem tawm cov qog nqaij hlav hauv cheeb tsam, thiab cov theem siab ntawm tus kab mob tuaj yeem tswj tau los ntawm kev kho tshuaj khomob nkaus xwb [31]. Hauv cov txheej txheem thauj khoom ntawm cov khoom siv lom neeg lom neeg, nws qhov kev nthuav dav tuaj yeem tsim kev cuam tshuam tsis zoo, uas yuav ua rau txo qis hauv kev ua haujlwm thiab kev tsis zoo [32]. Ntawm cov kev kho mob anticancer, cov kev kho mob yog qhov zoo tshaj plaws vim tias lawv muaj cov kev mob tshwm sim tsawg, muaj txiaj ntsig zoo, kev siv tshuaj tsawg, thiab kev kho mob tsis yooj yim rau nruab [33]. Piv txwv li, nanomedicine tau ntse siv los ua lub tsheb rau kev thauj mus los ntawm cov neeg ua haujlwm immunostimulatory los pab txhawb kev tiv thaiv kab mob tiv thaiv kab mob. Ntau lub tswv yim tau tshawb xyuas los txo cov tshuaj toxicity ntawm anticancer immunotherapy. Nano-formulations ntawm antigens, cytokines, chemokines, nucleotides, thiab tus xov tooj zoo li receptor agonists tau pom cov txiaj ntsig zoo [34]. Tam sim no, kev txheeb xyuas cov neeg ua haujlwm kho mob tshiab, uas muaj txiaj ntsig zoo dua thiab muaj kev cuam tshuam tsis zoo, tab tom ua rau muaj kev txaus siab ntxiv. Lub hom phiaj no yog qhov nyuaj kom ua tiav vim qhov nyuaj ntawm cov qog tsim tawm [35]. Monoclonal antibodies thiab chemoprevention los ntawm natural compounds yog ob qho tseem ceeb cov lus qhia rau kev kho mob thiab kev tiv thaiv ntawm cancer [36]. Ib qho ntawm cov tswv yim tseem ceeb hauv qhov no yog kev siv tshuaj lom neeg phytochemicals, vim tias lawv muaj cov tshuaj lom neeg tsawg thiab pleiotropic cuam tshuam hauv ntau cov txheej txheem ntawm tes uas cuam tshuam rau qhov pib thiab kev mob qog noj ntshav. Kev cuam tshuam nrog carcinogenesis los ntawm kev noj zaub mov lossis ntxiv nrog cov khoom xyaw ntuj hu ua chemoprevention [37-41]. Ntau tshaj 3000 tsob nroj teb nrog cov khoom tiv thaiv kab mob tau raug txheeb xyuas [42]. Ntawm cov compounds no,flavonoidsmuaj ntau tus neeg sawv cev nrog cov khoom cytotoxic rau ntau hom mob qog noj ntshav hauv tib neeg thiab tsis muaj lossis muaj kev cuam tshuam tsis zoo rau cov hlwb ib txwm [43]. Flavonoids yog polyphenolic tebchaw thiab sawv cev rau ib chav kawm ntawm biologically active metabolites nyob rau hauv cov nroj tsuag nrog ib tug yooj yim qauv ntawm diphenyl propane (C6-C3-}C6) thiab uas muaj ib tug tsawg molecular yuag. Lawv yog biosynthesized los ntawm phenylpropanoid thiab chalcones yog thawj flavonoids tsim [44-51]. Cov neeg ua ntej ntawm flavonoids yog phenylalanine, thiab calcium synthetase, calcium isomerase, thiab flavan 3 hydrolases yog suav tias yog cov enzymes tseem ceeb rau lawv cov biosynthesis [52-56]. Rau ntau flavonoids, tus choj tsim ib lub nplhaib pyranic lossis Byronic nplhaib [57]. Nyob ntawm cov qauv tsim, cov tshuaj no tau muab faib ua chalcones, aurones, flavanones, flavones, isoflavones, dihydroflavonols, flavonols, leucoanthocvanidins, anthocyanidins, thiab flavan-3-ols (Daim duab 1)[58-61].

Cov txheej txheem sib txawv ntawm cov tebchaw no tau los ntawm kev sib xyaw ua ke ntawm flavonoid biosynthesis enzymes nrog cov catalytic sib txawv thiab cov haujlwm tshwj xeeb [62]. Kev noj zaub mov ntawm flavonoids cuam tshuam nrog kev txo qis ntawm cov kab mob ntev, xws li kab mob plawv, kab mob neurodegenerative, mob hawb pob, kab mob autoimmune, thiab mob qog noj ntshav (tshwj xeeb tshaj yog mob ntsws, prostate, plab, thiab qog noj ntshav mis)[63-71]. Flavonoids kuj paub tias muaj ntau yam bioactivities, xws li tshuaj tiv thaiv kev ua xua, tshuaj tiv thaiv kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tiv thaiv kab mob, tiv thaiv kab mob, hepatoprotective, tiv thaiv kev rog, hormonal (xws li, estrogen zoo li kev ua haujlwm), thiab anti-aging prop-erties[72-85]. Muaj ntau cov kev tshawb fawb qhia tias flavonoids inhibit qhov kev loj hlob ntawm cov qog hlwb hauv vitro thiab hauv vivo [86]. Ntuj me me molecule tebchaw nyob rau hauv ib chav kawm ntawm flavonoids yog suav hais tias yuav muaj zoo kawg li physiological teebmeem, muaj tsis-mutagenic zog nyob rau hauv tib neeg lub cev, thiab tau attracted nce kev txaus siab rau kev txheeb xyuas cov tshuaj anticancer tshiab. Anticancer mechanisms ntawm flavonoids muaj xws li inhibiting cell loj hlob thiab proliferation los ntawm thaiv lub cell voj voog, inducing apoptosis thiab sib txawv, los yog combining cov mechanisms [87,88]. Tsis tas li ntawd, kev tshawb fawb txog kev kis mob qhia tau hais tias ntuj flavonoids muaj zog antioxidant muaj peev xwm cuam tshuam nrog kev mob qog noj ntshav tsawg [89,90]. Antioxidant kev ua ntawm flavonoids yog tshwm sim los ntawm lawv lub peev xwm los pub cov hydrogen atoms los ntawm hydroxy pawg mus rau dawb radicals, ib tug txheej txheem pab txhawb los ntawm kev txuas ntxiv conjugation tau muab los ntawm II electrons los ntawm flavonoids [91]. Flavonoids paub tias muaj lub peev xwm tseem ceeb antioxidant ntawm superoxide anions, hydroxyl radicals, thiab peroxy radicals. Tsis tas li ntawd, flavonoids zoo dua li ascorbic acid hauv neutralizing dawb radicals uas tsim los ntawm oxidative kev nyuaj siab [92]. Nyob rau hauv xyoo tas los no, cov tshuaj tiv thaiv kab mob ntawm flavonoids, tshwj xeeb tshaj yog lawv cov khoom antitimetastatic, tau lees paub thiab tshawb xyuas. Lawv lub peev xwm kho mob hauv kev kho mob qog noj ntshav tau qhia. Piv txwv li, LFG-500(C30H32N2O5) yog ib qho hluavtaws flavonoid nrog kev tiv thaiv kab mob thiab tiv thaiv qog noj ntshav. Cov tshuaj no kuj muaj peev xwm antitimetastatic 93]. Lub bioactivities ntawm flavonoids nyob ntawm seb lawv cov qib ntawm hydroxylation, cov txheej txheem chav kawm, xwm thiab txoj hauj lwm ntawm cov khoom uas twb muaj lawm, conjugations, thiab degree ntawm polymerization [94]. Muaj ntau cov khoom noj flavonoids muaj nyob rau hauv daim ntawv glycosidic, nyob rau hauv ib tug saccharide yog khi rau phenolic los yog hydroxy pawg ntawm cov compound [95,96]. Cov qauv ntawm saccharides yog ib qho kev txiav txim siab rau bioavailability ntawm flavonoids [97]. Flavonoids tam sim no yog cov khoom tseem ceeb ntawm ntau yam tshuaj, tshuaj pleev ib ce, thiab tshuaj tshuaj [98,99]. Qhov qis toxicity ntawm cov tebchaw no yog suav tias yog qhov zoo ntawm chav kawm no [100]. Qee zaum, glycosylation ntawm flavonoids yog lub luag haujlwm los txo cov tshuaj lom thiab tsis zoo ntawm cov tshuaj no [101].

Chalcones (13-diphenyl{1}}propen-1-ib qho) yog ib qho tseem ceeb tshaj plaws ntawm cov tshuaj flavonoids uas muaj nyob rau hauv txiv hmab txiv ntoo, zaub, thiab tshuaj yej [102] thiab sawv cev rau biogenetic precursors ntawm flavonoids thiab isoflavonoids [103]. Lawv yog lipophilic phytochemicals uas tsim los ntawm ob qho chaw uas muaj ntxhiab (ib qho aldehyde thiab acetophenone) koom nrog ib qho , -unsaturated carbonyl system ntawm peb carbon atoms (Daim duab 2) [102,104].

, pawg -unsaturated carbonyl yog ib tug zoo Michael txais thiab koom nrog nucleophilic ntxiv [105]. Chalcones muaj nyob rau hauv ob daim ntawv isomeric (cis thiab trans), qhov hloov pauv tau ntau dua thermodynamically ruaj khov thiab, implicitly, qhov tseem ceeb tshaj plaws configuration rau cov tebchaw (Daim duab 3) [106-108].

Qhov tseem ceeb ntawm cov tebchaw no yog los ntawm lawv cov chemistry yooj yim, lawv cov synthesis yooj yim, thiab lawv lub peev xwm los hloov ntau cov hydrogen atoms, yog li tsim ib tug loj tus naj npawb ntawm biologically active derivatives [109]. Ib qho tseem ceeb cuam tshuam nrog chalcones yog qhov ua tau ntawm cov tebchaw no kom yooj yim tsim cov pa roj carbon-carbon, carbon-sulfur, thiab carbon-nitrogen bonds, cov no yog precursors rau synthesis ntawm ntau yam heterocyclic tebchaw, xws li pyrimidines, pyridines, benzodiazepines, pyrazoles, 2-pyrazolines, imidazoles, thiab tag nrho lwm yam flavonoids|110-114. Isomerization ntawm chalcones rau cov flavanones sib xws nyob rau hauv muaj cov kua qaub lossis cov hauv paus piav qhia qhov tseem ceeb ntawm cov tebchaw no li ligands (Daim duab 4) [115]. Piv txwv li, Pandey et al. tau 5-nitro-flavanones los ntawm refluxing 2-hydroxy chalcones nyob rau hauv muaj cov concentrated sulfuric acid [116].

Vim lawv cov qauv hloov tau yooj yim, chalcones tuaj yeem khi rau ntau lub enzymes thiab receptors, uas piav qhia txog ntau yam kev siv roj ntsha ntawm cov tebchaw no [117]. Lwm qhov kev piav qhia rau cov haujlwm pharmacological ntawm cov tebchaw no yog kev sib txuas ntawm ob daim ntawv cog lus thiab pawg carbonyl tam sim no hauv cov qauv [118]. Lub bioactivities ntawm chalcones yog nyob ntawm txoj haujlwm, tus lej, thiab qhov xwm txheej ntawm cov khoom hloov pauv ntawm ob qhov seem uas muaj ntxhiab (aldehyde thiab acetophenone). Cov ntaub ntawv los ntawm cov ntaub ntawv qhia tau hais tias muaj pes tsawg tus ntawm ntuj thiab hluavtaws chalcones tau raug txheeb xyuas nrog kev siv tshuaj kho mob thiab tshuaj, cov tshuaj no muaj cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tua kab mob, tshuaj tiv thaiv kab mob Alzheimer's, tshuaj tiv thaiv kab mob, tiv thaiv kab mob HIV, antioxidant, antiulcer, estrogenic, thiab cov haujlwm neuroprotective. Chalcones muaj peev xwm inhibit -glucosidase, MAO-B (monoamine oxidase), tubulin, thiab tyrosine kinase [118-137]. Ntawm qhov tod tes, chalcones, nyob rau hauv tej yam kev mob, muaj oxidizing zog. Cov txiaj ntsig no tuaj yeem suav nrog kev ua haujlwm ntawm cov tshuaj tiv thaiv kab mob ntawm cov tshuaj no thiab ua raws li cov txheej txheem xws li kev tsim cov superoxide, cellular glutathione depletion, thiab phenoxide radical tiam. Tsis tas li ntawd, muaj cov kev tshawb fawb tau qhia txog kev ua haujlwm ntawm chalcones ntawm ntau kinases, microtubules, polytherapy-resistant proteins, thiab ntau yam kev taw qhia uas cuam tshuam nrog cell ciaj sia taus thiab tuag [138]. Cov qauv nthuav dav ntawm cov tebchaw no thiab ntau yam kev ua haujlwm lom neeg tau ua rau muaj kev pom zoo ntawm cov tshuaj tshiab los ntawm cov chav kawm chalcone, xws li metochalcone (cov tshuaj anticoleretic) thiab sofalcone (ib qho tshuaj tiv thaiv kab mob) (Daim duab 5) [139,140].

Cov ntaub ntawv los ntawm cov ntaub ntawv qhia tau hais tias kev hloov cov ntxhiab tsw ntawm chalcones nrog heterocycles txiav txim siab tsim cov molecules nrog cov khoom tshwj xeeb lom neeg [141].

Hybrid molecules muaj peev xwm daws tau qhov teeb meem ntawm kev tiv thaiv kev kho mob vim qhov tseeb tias sib txawv pharmacophores muaj ntau yam kev ua haujlwm. Vim hais tias hybridization ntawm molecules yog ib txoj hauv kev tseem ceeb rau kev txheeb xyuas cov tshuaj kho tshiab, muaj ntau cov hybrid molecules hauv kev sim tshuaj [142]. Piv txwv li, qhov kev taw qhia ntawm nitrogen atom haum rau hloov cov ntsiab lus ntawm molecules thiab txiav txim siab muaj peev xwm tsim cov ntawv cog lus muaj zog nrog lub hom phiaj. Lwm qhov tseem ceeb ntawm cov cuab yeej hloov kho yog polarity, uas tuaj yeem siv los txo cov lipophilic cwj pwm, ua rau solubilization hauv dej thiab kev nqus ntawm qhov ncauj [143].

Nws tau raug pom tias cov khoom siv roj ntsha muaj zog nrog cov nitrogen hauv cov molecules muaj cov khoom zoo tiv thaiv kab mob. Ntawm cov molecules nrog nitrogen, morpholines, thiab piperidines muaj cov dej num tseem ceeb ntawm ntau hom qog nqaij hlav [144]. Yadav et al. tau txais triazole chalcones nrog rau qhov tseem ceeb tshuaj tiv thaiv kab mob ntawm tib neeg cov kab mob [145]. Piv txwv ntawm qhov kev taw qhia ntawm cov tshuaj pharmacophore yog qhov zoo rau kev ua haujlwm lom neeg ntawm cov tebchaw yog qee cov hydride chalcones nrog cov seem ntawm quinazoline, biphenidate, thiab indole hauv cov molecules. Cov molecules tsim tshiab muaj peev xwm txiav txim siab qhov rov qab ntawm kev tiv thaiv rau kev kho mob cancer mis [146]. Nitrogen-hloov benzimidazole chalcones nrog alkyl residue los yog tsib-lossis rau-tus tswv cuab heterocycle kuj muaj cov teebmeem cytotoxic rau lub mis adenocarcinoma (MCF-7) thiab zes qe menyuam carcinoma (OVCAR-3). Lwm cov hydride molecules nrog cytotoxic kev ua ub no saum toj no cov qauv ntawm tib neeg cell kab (MCF-7, MA-PA-Ca2human pancreatic cancer hlwb, A549pulmonary adenocarcinoma, HepG2 human cancer cell kab) yog 1,2, 3-triazole chalcones. Hybrid thiazole tebchaw induce apoptosis los ntawm thaiv G2 / S theem ntawm lub voj voog ntawm tes thiab txo qis mitochondrial peev xwm ntawm MIA-PA-Ca2 cell kab hauv cov qog nqaij hlav pancreatic [147]. Kev tshawb fawb ntawm cov txheej txheem ntawm kev txiav txim rau 1,2A-triazole chalcones qhia tau hais tias lawv muaj peev xwm induce apoptosis los ntawm nce Bax protein ntau ntau, tso cytochrome C los ntawm mitochondria, thiab activating caspases 3, 8, thiab 9 [148]. Lub hom phiaj ntawm tsab xov xwm no yog los piav qhia cov ntaub ntawv tau txais kev sim thiab hauv silico txog kev ua haujlwm tiv thaiv kab mob ntawm qee qhov ntuj thiab hluavtaws chalcones.

2. Claisen-Schmidt Reaction

Txoj kev siv dav tshaj plaws kom tau cov chalcones hluavtaws yog Claisen-Schmidt condensation cov tshuaj tiv thaiv (Daim duab 6). Qhov no yog aldolization-colonization cov tshuaj tiv thaiv ntawm acetophenone derivatives nrog aromatic aldehydes. Cov tshuaj tiv thaiv tshwm sim hauv cov kua qaub lossis cov catalysis yooj yim nyob rau hauv homogeneous yam mob [149-152].

Kev siv cov alkaline nruab nrab yog qhov ua tau zoo dua kom tau txais chalcones [153]. Claisen-Schmidt condensation nyob rau hauv ib qho nruab nrab nruab nrab yuav tsim ib qho acetophenone anion tom qab los ntawm kev tawm tsam ntawm pawg carbonyl ntawm acetophenone [154]. Cov tshuaj tiv thaiv pib nrog cov txiaj ntsig ntawm 10 feem pua ​​​​thiab 60 feem pua. Condensation yog ua nyob rau ntawm 50 degree, cov tshuaj tiv thaiv lub sij hawm yog 12-15 h los yog ib lub lim tiam ntawm chav tsev kub [155]. Qhov tsis zoo ntawm txoj kev no yog qhov tsis muaj peev xwm rov qab tau cov catalyst, tsim cov khoom sib txuas ntxiv, tsis muaj kev xaiv, lub sijhawm ua haujlwm ntev, cov tshuaj tiv thaiv huab cua, thiab qhov nyuaj ntawm cov khoom sib cais [156]. Cov hom tshiab ntawm heterogeneous catalysts (Lewis acids, Bronsted acids, solid acids, thiab solid bases) tau raug txheeb xyuas rau cov synthesis ntawm chalcones nrog kev xaiv siab. Kev siv cov catalysts no zam kev cuam tshuam sab, xws li Cannizaro condensation cov tshuaj tiv thaiv lossis Michael ntxiv [157]. Tsis tas li ntawd, txhawm rau kom tsis txhob muaj qhov cuam tshuam tsis zoo ntawm aldehyde, tau sim hloov nws nrog benzylidene diacetate [155]. Lwm cov piv txwv ntawm cov tshuaj tiv thaiv kom tau txais chalcones yog Heck carbonylation coupling cov tshuaj tiv thaiv, Sonogashira isomerization, thiab cov tshuaj tiv thaiv sib txuas, cov tshuaj tiv thaiv tsis tu ncua, Suzuki-Myaura coupling cov tshuaj tiv thaiv, thiab cov tshuaj tiv thaiv synthesis mediated los ntawm cov kua qaub catalyst [{12}}].

Nyem qhov link kom tau qhov 2:https://www.xjcistanche.com/news/part2-anticancer-activity-of-natural-and-synt-54977563.html

Nyem qhov link kom tau qhov 3:https://www.xjcistanche.com/news/part3-anticancer-activity-of-natural-and-synt-54978140.html