Camptothecin, hu ua CPT, yog ib yam khoom ntuj tsim, thiab nws cov qauv tshuaj muaj cov pa oxygen uas muaj ntxhiab tsw thiab ib lub nplhaib hydrophilic monocyclic tetraazine benzofuran. CPT yog qhov sib xyaw ua ke nrog cov haujlwm tseem ceeb lom neeg. Nws tau pom tias muaj cov haujlwm tseem ceeb hauv kev tiv thaiv kabmob kheesxaws thiab yog cov tshuaj tiv thaiv kabmob tseem ceeb heev. Txawm li cas los xij, tej yam ntuj tso ntawm CPT yog qhov tsawg heev, thiab seb CPT puas tuaj yeem tau los ntawm kev siv tshuaj lom neeg tsis muaj kev txwv ntawm cov peev txheej ntuj ib txwm yog qhov teeb meem kub ntawm kev txhawj xeeb rau cov kws tshawb fawb. Daim ntawv no qhia txog tag nrho cov txheej txheem synthesis ntawm CPT tam sim no.
1. Natural source synthesis:
CPT yog thawj zaug cais tawm ntawm kev lag luam sab qab teb fern Camptotheca acuminata. Cov ntsiab lus CPT ntawm cov nroj tsuag no tsawg heev, yog li cov peev txheej ntuj tsis tshua muaj kev txwv. Tsis tas li ntawd, lwm cov nroj tsuag thiab cov kab mob microbes kuj pom muaj cov kab mob CPT, tab sis nyob rau hauv ntau tsawg thiab tsawg.
2. Sib cais CPT:
Vim muaj kev txwv tsawg heev ntawm CPT los ntawm cov peev txheej ntuj, cov kws tshawb fawb tau tshawb xyuas ntau txoj hauv kev los npaj CPT.
(1) Gilbert synthesis
Xyoo 1966, Gilbert thawj zaug tau tshaj tawm cov txheej txheem ntawm kev sib txuas ntawm CPT los ntawm kev ua haujlwm p-methoxyphenethylamine nrog -keto acid lossis nws cov ester los ntawm lub nplhaib kaw cov tshuaj tiv thaiv. Cov tshuaj tiv thaiv no tsim ib qho nruab nrab hu ua 2-(2-methoxyethoxy)ethylisoxazole (EAO), uas tuaj yeem sib xyaw ua CPT.
(2) Fukuyama synthesis
Xyoo 1996, Fukuyama tau npaj ib txoj hauv kev tshiab los npaj CPT los ntawm kev siv lub zog electrophilic fluoride ion reagent thiab dianthrone derivative li reactants. Nyob rau theem pib ntawm cov tshuaj tiv thaiv, thawj amine tiv thaiv pab pawg raug tshem tawm los ntawm decomposition los tsim cov enol ntawm lub davhlau ya nyob twg unsaturated daim ntawv cog lus, yog li inducing lub CPT kom tau cov synthesis ntawm lub polycyclic system.
(3) Mannich synthesis
Xyoo 2002, Kuehne thiab Hofheinz^ ua ke CPT los ntawm Mannich cov tshuaj tiv thaiv, uas siv catechol thiab diaryl ketone thiab formaldehyde ua reactants, thiab siv cov kua qaub ua catalyst.
(4) Moura-Letts synthesis
Xyoo 2015, Moura-Letts tau npaj CPT los ntawm Mannich thiab Diels-Alder cov tshuaj tiv thaiv siv piperidine acetate hydrochloride thiab lwm yam reactants.
3. Semi-synthetic CPT:
Semi-synthetic CPT siv CPT derivatives ua cov ntaub ntawv pib thiab dhau los ua cov tshuaj sib txawv los tsim cov CPT derivatives uas muaj peev xwm ua tau. Semi-synthetic CPT muaj qhov muaj txiaj ntsig ntawm kev sib txawv thiab yog ib txoj hauv kev siv ntau hauv cov organic synthesis.
(1) Topotecan thiab Irinotecan
Ntawm cov semi-synthetic CPTs, Topotecan thiab Irinotecan paub zoo tshaj plaws. Ob lub tebchaw no yuav ua rau muaj kev sib cav ntxiv los tsim cov derivative SN-38, uas muaj peev xwm ua haujlwm hauv kev kho mob qog noj ntshav. Cov tebchaw no tsim cov qauv molecular sib txawv los ntawm kev hloov pauv sib txawv ntawm 2'-hydroxyethyl thiab 10-acyl pawg. Hauv kev kho mob, Topotecan thiab Irinotecan tau raug pov thawj tias yog cov tshuaj zoo hauv kev kho mob ntawm zes qe menyuam thiab mob qog noj ntshav.
(2) 4 -hydroxy CPT
4 -Hydroxy CPT yog CPT synthesized los ntawm ib tug semi-synthetic txoj kev. Thawj qhov kev hloov kho ntawm CPT yog ntxiv ib pab pawg hydroxyl mus rau 4- txoj haujlwm. Cov tshuaj no muaj cov tshuaj toxicity qis, yooj yim los lis, thiab yooj yim rau crystallize ntawm tsawg concentrations.
(3) 10-(N, N-Dimethylamino) CPT
Xyoo 1969, Chen thiab ob pawg neeg tshawb fawb tau hais txog qhov saturated CPT derivative, 10-(N, N-dimethylamino) CPT. Cov derivative muaj ntau dua dej solubility thiab muaj zog bioavailability, thiab muaj kev kho mob zoo dua piv nrog CPT.
4. Lwm txoj kev hluavtaws:
Muaj qee qhov kev sib txuas ntawm CPT xws li: Kuehne synthesis (los ntawm Regina Kuehne thiab Hiller), Friedländer synthesis (thawj qhia los ntawm Hans Friedländer), linear synthesis thiab lwm yam. Txij li cov txheej txheem no tsis meej txaus, peb yuav tsis piav qhia lawv.
Hauv cov ntsiab lus, tag nrho cov txheej txheem hluavtaws tam sim no ntawm CPT tau raug sau ua ke thiab lawv qhov zoo thiab qhov tsis zoo tau muab. Txawm hais tias cov khoom siv ntawm CPT los ntawm cov peev txheej ntuj raug txwv, los ntawm ntau txoj hauv kev tshuaj, ntau tus CPT derivatives tuaj yeem ua ke, uas xav kom muab cov kev xaiv zoo dua rau kev kho mob qog noj ntshav.
Camptothecin yog cov tshuaj lom tshwj xeeb alkaloid nrog ntau yam tshuaj tiv thaiv qog noj ntshav, tshwj xeeb tshaj yog nyob rau hauv daim siab mob qog noj ntshav, mob qog noj ntshav, mob ntsws cancer, mob qog noj ntshav ntawm zes qe menyuam, leukemia thiab lwm yam. Nws cov tshuaj tiv thaiv qog nqaij hlav feem ntau yog los ntawm inhibiting cov haujlwm ntawm topoisomerase I (Top1), kom DNA ntawm cov qog hlwb tsis tuaj yeem rov ua dua, ua rau cov qog hlwb tuag.
Tsis tas li ntawd, Camptothecin tseem muaj cov nyhuv immunomodulatory, uas tuaj yeem tswj cov haujlwm ntawm lub cev tiv thaiv kab mob xws li T thiab B lymphocytes thiab macrophages, thiab txhim kho lub cev tiv thaiv kab mob.