Cisplatin hmoov, tshuaj hu ua cis-dichlorodiammine platinum divalent complex hmoov, yog ib lub txiv kab ntxwv cis - daj zoo crystalline hmoov. Nws yog lub ntiaj teb thawj cov hlau-kev sib koom tes- hom tshuaj tiv thaiv kab mob ua kom muaj kev ua tiav loj - daim ntawv thov. Tom qab recrystallization thiab purification, cov khoom tiav muaj ruaj khov HPLC purity tshaj 99.5%, nrog hnyav hlau impurities thiab trans isomer cov ntsiab lus nruj me ntsis tswj nyob rau hauv pharmacopoeia txwv. Lub hauv paus tseem ceeb ntawm cov hmoov no yog lub hom phiaj tetragonal platinum coordination molecule. Nws ua tiav intracellular activation los ntawm qhov tshwj xeeb hydrolyzable chloride ligand ntawm cis - kev sib koom ua ke, tsom mus rau ob - tso tseg DNA ntawm cov qog hlwb los tsim cov ntoo khaub lig irreversible - txuas kev puas tsuaj, ib txhij ua kom muaj ntau yam apoptosis kev tswj hwm txoj hauv kev, thiab nthuav tawm txoj hauv kev tawm tsam {1} kev tshuaj lom neeg sai sai. proliferating khoom qog hlwb.
🧪 Planar rectangular coordination moj khaum thiab spatial structural nta
Cisplatin hmoovmuaj divalent platinum ion raws li lub hauv paus kev koom tes atom ntawm nws cov tub ntxhais. Plaub dsp² hybrid orbitals tsim ib lub hom phiaj xwm txheej square spatial configuration. Ob lub amino ligands thiab ob chloride ligands yog tag nrho cov txheej txheem nyob rau tib sab ntawm lub dav hlau nyob rau hauv ib tug cis configuration. Cov mis mos molecular tiav yog Pt (NH₃)₂Cl₂, nrog cov txheeb ze molecular loj ntawm 300.60. Ib qho -crystal X-ray diffraction qauv tuaj yeem txiav txim siab qhov ntev thiab daim ntawv cog lus ntawm platinum atoms thiab ligands. Lub platinum-nitrogen daim ntawv cog lus ntev yog ruaj khov ntawm 202 picometers, thiab lub platinum - chlorine daim ntawv cog lus ntev yog 232 picometers, nrog rau lub kaum sab xis ntawm qhov sib txawv tsis ntau tshaj 0.8 degrees. Lub molecule tag nrho tsis muaj peb - qhov ntev folded qauv thiab muaj nyob ntawm nws tus kheej nyob rau hauv ib tug nruj planar configuration. Tom qab crystallization, cov hmoov hais yog uniformly faib thiab tsis muaj molecular stacking los yog agglomeration. Lub trans-dichlorodiammineplatinum, sib txawv tsuas yog nyob rau hauv ligand kev npaj, muaj chloride ligands faib kab pheeb ces kaum nyob rau hauv lub dav hlau, ua rau nws tsis muaj peev xwm ua tau zoo intracellular hydrolysis thiab DNA cross-txuas. Nyob rau tib lub molar concentration, nws cov qog cell tua efficiency tsawg dua tsib feem pua ntawm cov cis{19}}molecule. Kev sib koom ua ke ntawm spatial yog ib qho tseem ceeb hauv kev mob rau cov molecule txoj kev ua haujlwm antitumor.
Ob hom ligands nyob rau hauv lub molecule muaj cov tshuaj sib txawv kiag li. Cov amino ligands ruaj khov rau hauv nruab nrab platinum ion, tiv thaiv kev sib cais thiab tso tawm hauv ib puag ncig physiologically buffered. Ob lub chloride ligands muaj zog daim ntawv cog lus tsis muaj zog, tso cai rau kev ua kom muaj zog hydrolysis thiab kev hloov pauv hauv ib puag ncig aqueous. Chloride ions raug hloov los ntawm cov dej molecules los tsim kom muaj txiaj ntsig zoo ntawm platinum hydrate nruab nrab. Cov txheej txheem reversible hydrolysis no yog thawj kauj ruam hauv kev pib DNA kev puas tsuaj tom qab cov molecule nkag mus rau cov qog hlwb. Ib txheej ntawm hydrolysis kinetic cov ntaub ntawv qhia tau hais tias tom qab plaub teev ntawm cia ntawm 25℃nyob rau hauv nruab nrab dej, kwv yees li 42% ntawm cov hmoov molecules underwent monochlorination hydrolysis. Tom qab 18 teev, qhov kev faib ua feem ntawm dichlorination active intermediates tau nce mus rau 76%. Lub qeeb hydrolysis tus nqi nyob rau hauv lub cev osmotic siab ua kom cov molecules nyob twj ywm nyob rau hauv ib tug ruaj khov, inactive lub xeev ua ntej hla cell membranes, thiab tsuas yog activated tag nrho thaum lawv nkag mus rau hauv qis -chloride microenvironment nyob rau hauv lub hlwb, txo qhov tshwm sim ntawm indiscriminate kev puas tsuaj rau ib txwm somatic hlwb.
Cov hmoov crystallization cia siab rau qhov tsis muaj zog van der Waals quab yuam ntawm cov molecules, tsis muaj kev sib txuas ntawm covalent ntoo khaub lig- txuas cov qauv. Nws cov dej solubility yog kom meej meej txwv, nrog ib tug solubility ntawm tsuas yog 2.53 g / L nyob rau hauv cov dej ntshiab ntawm 25 degree. Nyob rau hauv siab -chloride buffer system, solubility tuaj yeem nce ntau dua peb zaug. Qhov siab -chloride ib puag ncig inhibits hydrolysis ntawm chloride ligands, txuas ntxiv lub sijhawm ruaj khov ntawm cov khoom siv tsis siv neeg. Cov hmoov ua tiav tuaj yeem khaws cia ruaj khov rau 24 lub hlis hauv qhov chaw kaw, lub teeb - pov thawj, thiab ib puag ncig qhuav. Thaum lub sij hawm cia, qhov nce hauv trans isomer impurities tsawg dua 0.25%. Kub kub thiab ncaj qha tshav ntuj ua kom muaj kev sib koom ua ke ntawm kev sib koom ua ke, maj mam hloov cov cis teeb tsa mus rau qhov tsis muaj zog trans qauv. Tom qab 30 hnub ntawm qhov kub thiab txias thiab qhib cia ntawm 50 degrees Celsius, qhov kev faib ua feem ntawm cov active molecules txo mus rau 71%, thiab kev puas tsuaj ntawm crystal stacking qauv tshwm sim ib txhij nrog configurational isomerization.
Muaj ob qhov chaw electrophilic reactive nyob rau ntawm ntug ntawm lub dav hlau molecular, sib haum mus rau ob qho kev sib koom ua ke orbitals tom qab hydrolysis thiab tso tawm chloride ions. Qhov kev ncua deb ntawm ob qhov chaw raws nraim qhov sib txawv ntawm qhov chaw nyob ze ntawm guanine N7 nitrogen atoms hauv qhov loj ntawm DNA ob lub helix. Qhov 290 picometer qhov sib nrug ntawm ob qhov chaw nquag tuaj yeem khi ob lub hauv paus purine, ua kom ruaj khov intrachain cross-txuas kev sib txuas. Ib leeg-site hlau complexes tsuas tuaj yeem tsim ib zaug xwb- taw tes DNA khi thiab tsis tuaj yeem cuam tshuam cov qauv ntawm ob lub helix spatial, yog li txo qis lub voj voog ntawm tes raug ntes. Lub symmetrical kev npaj ntawm planar square dual active qhov chaw yog lub ntsiab yam ntxwv zoo ntawm cov hmoov no nyob rau hauv zoo thaiv DNA replication thiab transcription. Piv nrog cov monodentate coordination hlau raw cov ntaub ntawv, tus nqi ntawm DNA cross-txuas cov khoom tsim nyob rau tib qhov zoo concentration yog nce 4.6 npaug.
⚙️ Hydrolysis-activated DNA cross- txuas induces qog cell apoptosis
Cisplatin hmoov tswj cov hluav taws xob nruab nrab thiab tsis muaj kev sib koom ua ke ua ntej nkag mus rau hauv cov hlwb. Lub siab chloride ion extracellular kua ib puag ncig inhibits chloride ligand hydrolysis, thiab cov molecule hla ntawm phospholipid bilayer tsis ntxov ntxov ua kom nquag plias intermediates, zam tsis yog - tshwj xeeb covalent hloov kho rau cell membranes thiab extracellular matrix proteins. Cov molecule ua tiav intracellular enrichment los ntawm passive diffusion thiab synergistic nkaus nrog CTR1 transporter. Cov tshuaj chloride ion concentration nyob rau hauv cov qog hlwb tsuas yog ib qho -quarters ntawm sab nraud. Qhov qis no -chloride microenvironment tam sim ntawd pib cov tshuaj tiv thaiv hydrolysis stepwise. Thawj chloride ion yog hloov los ntawm cov dej molecules los tsim ib qho monochloroplatinum hydrate cation intermediate. Tom qab ntawd, qhov thib ob chloride ion yog hydrolyzed thiab tso tawm, tsim ib tug heev electrophilic platinum dihydrate active core. Ob qhov kev sib koom ua ke khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob. Tag nrho cov txheej txheem ua kom tsis muaj tshuaj lom me me los ntawm cov khoom lag luam, tsuas yog tso cov tshuaj dawb chloride ions dispersed nyob rau hauv lub cytoplasmic system.
Cov activated platinum dihydrate intermediate migrate directionally mus rau hauv lub cell nucleus, precisely embedding mus rau hauv lub loj groove cheeb tsam ntawm DNA ob helix. Ob qhov kev sib koom ua ke khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob khoob Ib qho me me ntawm cov molecules tuaj yeem hla ob DNA strands los ua cov kab sib txuas sib txuas -txuas, thiab covalent daim ntawv cog lus ruaj khov kho qhov sib txawv ntawm ob lub helix. Ib txwm DNA replication thiab transcription yuav tsum tau muab ob npaug rau helix unwinding thiab puag khub sib cais. Tus ntoo khaub lig- txuas kev cuam tshuam tag nrho thaiv helicase thiab polymerase los ntawm kev khi rau cov qauv strand, mus tas li nres DNA replication ntawm S-theem. Cov qog nqaij hlav tsis tuaj yeem ua tiav cov khoom siv caj ces nthuav dav, thiab lub voj voog loj hlob yog cuam tshuam tag nrho. Nyob rau hauv vitro DNA electrophoresis cov ntaub ntawv qhia tau hais tias tom qab co{12}}incubating ob -stranded DNA nrog ib tug 0.01 mmol / L concentration ntawm hmoov rau kaum ob teev, tshaj 83% ntawm cov DNA molecules tsim ruaj khov cross- txuas bands, tsis muaj dawb, zoo li qub ob npaug -stranded DNA.
DNA cross- txuas kev puas tsuaj txuas ntxiv ua rau ntau txoj hauv kev puas tsuaj rau hauv lub cev. Genomic aberration signals raug lees paub los ntawm ATM protein kinases, nce qib nce kev qhia ntawm p53 qog suppressor protein. p53 ces nkag mus rau hauv lub nucleus los tswj cov transcription ntawm pua pua ntawm apoptosis-cov noob caj noob ces, upregulating pro-apoptotic Bax protein thiab downregulating anti-apoptotic Bcl2 protein. Mitochondrial membrane permeability yog nce zuj zus, thiab cytochrome C raug tso tawm rau hauv cytoplasm, ua kom cov tshuaj tiv thaiv caspase cascade shearing, thaum kawg pib programmed cell tuag. Ntxiv nrog rau txoj kev puas tsuaj rau DNA nuclear, cov tshuaj platinum reactive intermediates tuaj yeem cuam tshuam ncaj qha rau mitochondrial matrix, ua rau mitochondrial ncig DNA thiab inducing ib tug loj tsub zuj zuj ntawm reactive oxygen hom. Ntau dhau dawb radical oxidation puas tsuaj rau mitochondrial respiratory chain proteins, amplifying apoptosis signals. Cov kev puas tsuaj ob txoj hauv kev sib koom ua ke txhim kho qog cell clearance efficiency.
Intracellular antioxidant sulfhydryl molecules tsim ib qho kev tiv thaiv ntuj. Glutathione thiab metallothionein tuaj yeem koom tes nrog reactive platinum intermediates, neutralizing lawv electrophilic kev ua si thiab ua kom lawv tshem tawm ntawm lub cell. Cov txheej txheem no yog lub hauv paus ntsiab lus ntawm innate los yog kis tau cov qog tshuaj tiv thaiv. Cov qog hlwb raug rau cov hmoov rau lub sij hawm txuas ntxiv tau nthuav tawm ntau dua ob npaug ntawm kev sib txuas ntawm cov glutathione intracellular, ua rau muaj kev cuam tshuam loj ntawm cov platinum molecules, txo qis hauv DNA cross- txuas cov khoom tsim, thiab cov cim txo qis hauv apoptosis. Txoj kev tsom xam ntawm qhov kev kam rau siab no siv siab -purityCisplatin hmoovraws li tus txheej txheem inducing substrate, ua kom tswj tau kev tsim kho ntawm cov tshuaj ruaj khov -cov qauv qog cell. Qhov no tso cai rau qhov kev txiav txim ncaj qha ntawm qhov nruab nrab thiab inhibitory cuam tshuam ntawm thiol-raws li antioxidant molecules ntawm platinum-raws li molecules, muab cov ntaub ntawv qhia txog kev txhawb nqa rau kev tsim cov hlau lead tshiab rau kev txo cov tshuaj lom thiab thim rov qab tshuaj tiv thaiv.
🧫 Ntau- cov ntawv siv qhov loj me hauv thaj chaw biomedical
Cov kev siv tseem ceeb ntawmCisplatin hmoovyog concentrated nyob rau hauv lub elucidation ntawm molecular pharmacological mechanisms nyob rau hauv cov qog nqaij hlav. Ntau yam hauv vitro cell qauv hais txog kev puas tsuaj genomic, apoptosis, thiab qog cov tshuaj tiv thaiv tag nrho tso siab rau cov hmoov no ua tus qauv zoo inducing substrate. Kev ntsuam xyuas cov qog tshuaj pharmacological yooj yim yuav tsum muaj kev ruaj ntseg thiab tswj tau DNA kev puas tsuaj stimuli. Feem ntau cov khoom siv hluavtaws alkylating muaj dav - spectrum hloov kho cov protein tsis xws luag, uas ib txhij cuam tshuam cov kab mob hauv lub cellular thiab cuam tshuam nrog cov ntaub ntawv tshawb nrhiav txoj hauv kev. Cov hmoov no tshwj xeeb tshaj yog tsom rau cov purine hauv paus los tsim cov ntoo khaub lig- txuas, yam tsis muaj kev hloov pauv tseem ceeb ntawm cytoplasmic dawb proteins, uas ua rau muaj kev cuam tshuam yav dhau los tsawg heev. Kev tswj cov ntaub ntawv zoo sib xws los ntawm ntau lub chaw muag tshuaj R&D platforms qhia tias kev siv cov hmoov no los tsim cov qauv DNA puas ntawm tes txo qhov kev ua yuam kev ntawm cov ntaub ntawv qhia txog txoj kev tshawb pom los ntawm 62%, tshem tawm qhov xav tau rau ntau- txheej txheej tswj pawg kom tsis suav nrog cov tsis yog -cov protein tshwj xeeb hloov pauv cuam tshuam, thiab ua kom yooj yim 10 kev puas tsuaj rau cov txheej txheem - mechanisms.
- Kev tsim kho ntawm cov qauv hauv vitro ntawm DNA kev puas tsuaj teb txoj hauv kev hauv cov qog nqaij hlav
- Platinum{0}}raws li antitumor lead molecule kev ua ub no tswj substrate
- Inducing khoom rau innate thiab tau txais tshuaj tiv thaiv mechanisms nyob rau hauv cov qog hlwb
- Standardized reference qauv rau cov qauv-kev sib raug zoo ntawm hlau-coordinated anticancer tshuaj
Kev sib piv kev soj ntsuam ntawm qhov ua tau zoo ntawm ntau yam khoom siv lead ua molecules yog qhov thib ob core daim ntawv thov scenario ntawm cov hmoov. Txoj kev loj hlob ntawm cov tshiab active hlau complexes thiab organic targeted molecules rau siab - tshwm sim cov qog nqaij hlav xws li qog noj ntshav ntawm zes qe menyuam, testicular kab mob qog noj ntshav, tsis yog -mob cell ntsws cancer, lub taub hau thiab caj dab squamous cell carcinoma, thiab mob qog noj ntshav tag nrho siv Cisplatin hmoov raws li kev siv tshuaj sib piv benchmark. Hauv vitro qog cell ib nrab-qhov siab tshaj plaws inhibitory concentration (IC50) tuaj yeem txheeb xyuas qhov muaj peev xwm tua cov tshiab molecules. Cov ntaub ntawv los ntawm peb qhov -cov qog nqaij hlav spheroid kab lis kev cai qhia tau hais tias nyob rau ntawm qhov ntsuas molar concentration, cov hmoov no tuaj yeem txo qhov ntim ntawm cov qog spheroids ze li 60%. Raws li kev sib koom ua ke, nws tso cai rau kev sib piv kab rov tav ntawm cov qog{10}} inhibiting kev ua tau zoo ntawm cov kab mob sib txawv ntawm cov pob txha active molecules, ua rau nws yog ib qho tseem ceeb ntawm cov khoom siv tshuaj tsis tseem ceeb hauv kev tshuaj ntsuam thawj zaug ntawm cov tshuaj antitumor lead molecules.
Cov hmoov no yog siv dav hauv kev tshuaj xyuas ntawm cov khoom siv molecules rau thim rov qab cov tshuaj tiv thaiv qog. Tom qab tsis tu ncua incubating hmoov los tsim cov tshuaj ruaj khov -cov kab mob qog ntawm tes, nws yog siv los soj ntsuam cov kev tswj xyuas ntawm ntau yam me me molecules, peptides, thiab natural extracts ntawm reversing platinum kuj. Tshuaj-cov tshuaj tiv thaiv kab mob ua rau pom qhov txawv txav ntawm glutathione transporter thiab DNA kho enzymes. Novel reversal molecules tuaj yeem txo qis cov proteins antioxidant, inhibit DNA puas kho txoj hauv kev, thiab kho cov qog cell rhiab heev rau platinum-raws li molecules. Tag nrho cov kev ntsuam xyuas yuav tsum cia siab rau siab -purity, impurity-dawb hmoov los tsim ib tug ruaj khov tshuaj- phenotype resistant; impurities tuaj yeem cuam tshuam nrog kev qhia ruaj khov ntawm txoj hauv kev ntawm cov cellular kam rau ua, ua rau muaj kev cuam tshuam ntawm kev sib piv cov ntaub ntawv siv tshuaj.
Cisplatin hmoovyog dav siv nyob rau hauv kev ua tau zoo tus yam ntxwv ntawm cov hlau - phiaj xa khoom nqa. Liposomes, polymer nanogels, thiab peptide- hloov kho cov hlau nanoparticles tag nrho siv cov hmoov no ua cov qauv active core cov ntaub ntawv kom quantitatively ntes carrier encapsulation efficiency, intracellular tso efficiency, thiab qog nqaij hlav enrichment peev. Cov hmoov molecules muaj cov yam ntxwv ntawm ultraviolet absorption spectra thiab platinum element mass spectrometry signals, tso cai rau kom muaj nuj nqis ntawm cov ntsiab lus molecular zoo ntawm cov cab kuj xa mus rau cov hlwb thiab cov ntaub so ntswg. Kev sib piv nrog ib pab pawg neeg nqa khoom dawb tuaj yeem tshawb xyuas ncaj qha rau cov tshuaj toxicity -txo thiab ua tau zoo- txhim kho kev ua haujlwm ntawm cov neeg nqa khoom, ua rau nws ua tus qauv tseem ceeb rau kev tsim cov khoom siv tshuaj nanodelivery.
🔬 Coordination molecule modification and novel adaptation development
Kev nce qib txuas ntxiv hauv kev hloov pauv thiab hloov kho ntawm Cisplatin hmoov ligands. Raws li lub hauv paus ntsiab lus ntawm kev sib koom ua ke ntawm cov phiaj xwm square platinum, ob lub chloride ligands hloov nrog inert ligands ntawm carboxylic acids thiab heterocyclic amines los tswj cov intracellular hydrolysis tus nqi thiab ib txwm somatic cytotoxicity. Ntuj chloride ligands hydrolyze sai heev, yooj yim tsim active intermediates nyob rau hauv lub raum tubular hlwb thiab ua rau lub cev puas tsuaj. Hloov kho platinum molecules, tom qab hloov cov inert, hydrolyzable ligands, maj mam tso cov active platinum core tsuas yog nyob rau hauv lub acidic qog microenvironment. Raws li tib lub qog- cov nyhuv cuam tshuam, qhov feem pua ntawm lub raum kev puas tsuaj yog txo los ntawm ntau dua 70%. Cov hloov tshiab tshiab platinum complex hmoov yog maj mam nkag mus rau cov txheej txheem sib piv rau qis -toxicity antitumor lead molecules.
Targeted functional ligand coupling hloov kho ntawm cov hmoov yog ib qho tseem ceeb optimization mus kom ze tam sim no tab tom nrhiav. Qhov no suav nrog grafting qog- tshwj xeeb receptor paub peptides thiab hyaluronic acid lub hom phiaj fragments mus rau qhov kawg ntawm cov amino ligands los tsim platinum-kev sib koom ua ke hybrid molecules nrog tsim- nyob rau hauv qhov txhab- phiaj xwm kev paub. Hloov cov hmoov molecules conjugated nrog lub hom phiaj ligands tuaj yeem txuas rau cov receptors zoo heev ntawm cov qog cell membranes, txhim kho qhov ua tau zoo ntawm kev ua haujlwm ntawm cov qog hlwb. Ib txheej ntawm peb-qhov loj me ntawm cov qog spheroid permeation tswj cov ntaub ntawv qhia tau hais tias qhov concentration ntawm peptide- cov phiaj xwm hloov pauv hauv qhov txhab tau nce 2.8 npaug. Raws li tib lub qog-tshuaj nyhuv, cov molar concentration ntawm cov khoom siv raw yuav raug txo los ntawm ze li ntawm 70%, txo cov kab mob hauv nruab nrog cev kev ntxhov siab vim los ntawm lub sij hawm ntev - raug rau siab -concentration hlau molecules, thiab ua rau nws tsim nyog rau kev loj hlob ntawm tsawg- koob tshuaj, kev cuam tshuam ntev -.
Kev tsim kho ntawm bimetallic synergistic kev sib koom ua ke hybrid molecules tau dhau los ua qhov kev tsim kho tshiab. Lub core platinum coordination unit ntawm Cisplatin yog covalently txuas nrog rau lwm yam khoom muaj nqi hlau anticancer fragments xws li palladium thiab ruthenium los ntawm saj zawg zog txuas chains los tsim ib tug tib - molecule bimetallic active center hybrid active tshuaj. Bimetallic molecules muaj ob txoj kev ywj pheej DNA kev puas tsuaj: platinum units kho ob -strand cross- txuas, thaum ruthenium units induce mitochondrial oxidative puas. Ob txoj kev tua neeg no tsis yog -antagonistic, tswj kev ruaj khov cytotoxicity tiv thaiv ntau-platinum- cov qog hlwb tiv taus. Hauv qhov sib piv, tib cov hmoov platinum tsuas yog ua rau tib lub hom phiaj DNA. Cov hybrid bimetallic molecule nthuav tawm ze li ntawm 50% zoo dua inhibition ntawm cov tshuaj- tiv thaiv kab mob piv rau thawjCisplatin hmoov, ua kom yooj yim cov txheej txheem raw khoom tsim rau ntau- yeeb tshuaj- tiv thaiv qog ua haujlwm ua haujlwm.
Inert, hydrolyzable ligand hloov txo cytotoxicity rau lub cev.
- Cov qog nqaij hlav-kev tsom mus rau peptide grafting txhim khu kev ua kom muaj txiaj ntsig zoo hauv cov kab mob.
- Dual noble hlau tandem hybrid molecules kov yeej qog platinum kuj.
- Microenvironment- teb kev sib koom ua ke prodrug molecules tau txais kev hloov pauv hloov pauv.
Kev ua kom zoo ntawm cov hmoov microenvironment- teb cov tshuaj prodrug molecules tau siv tas li. Kev hloov kho rau lub hauv paus kev sib koom tes caj qaum qhia pH-sensitive ester bonds thiab enzyme-cleavable peptide chains los npog lub platinum active chaw. Lub cev tsis muaj zog prodrug tsis muaj peev xwm ua kom muaj peev xwm ua rau cov ntaub so ntswg tsis zoo, tsuas yog tawg thiab tso cov platinum ua haujlwm thaum ncav cuag cov kua qaub, siab -protease microenvironment ntawm cov qog. Tag nrho cov lus teb prodrug system ua kom tsis txhob muaj qhov tsis yog- tshwj xeeb hydrolysis thiab ua kom muaj zog hauv cov hlwb somatic ib txwm, txo qis qhov tshwm sim ntawm ototoxicity thiab nephrotoxicity tshwm sim ntawm cov hmoov, thiab txhim kho kev sib raug zoo nrog cov qog-txog cov kev ntsuam xyuas yooj yim rau cov neeg laus thiab cov neeg uas muaj lub cev tsis muaj zog ntawm kev ua haujlwm ntawm lub cev, Cisplatin hmoov.
Xaus
Cisplatin hmoov yog cov hlau tsis muaj zog-raws li cov tshuaj hauv keeb kwm ntawm kev kho mob qog noj ntshav niaj hnub no. Nws cisplatin-amine coordination qauv yog lub hauv paus molecular rau nws tshwj xeeb intra- saw cross- txuas nrog DNA. Cov nyhuv "rivet" no tso cai rau nws los thaiv DNA replication hauv qog hlwb, coj lawv mus rau apoptosis. Los ntawm kev kho mob qog noj ntshav mus rau kev sib txuas tshuaj kho mob rau ntau yam qog nqaij hlav xws li qog nqaij hlav zes qe menyuam thiab lub taub hau thiab caj dab, cisplatin tau tsim nws txoj haujlwm tseem ceeb hauv thaj tsam ntawm kev tiv thaiv - cov tshuaj qog noj ntshav.
Xi'an Faithful BioTech Co., Ltd. siv cov cuab yeej siv siab heev thiab cov txheej txheem los xyuas kom meej - cov khoom zoo. PebCisplatin hmoovua tau raws li cov qauv tshuaj thoob ntiaj teb. Peb nrhiav kev ua tau zoo, tus nqi tsim nyog, thiab kev pabcuam zoo tshaj plaws ua rau peb nyiam tus khub rau cov tsev kho mob thiab cov kws tshawb fawb thoob ntiaj teb. Yog tias koj xav tau Cisplatin hmoov tshawb fawb lossis kev tsim khoom, thov hu rau peb pab neeg ua haujlwm ntawmallen@faithfulbio.com.
Cov ntaub ntawv
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