SN-38 loaded multi-target drug carrier and application thereof
A multi-targeting, drug technology, applied in the direction of drug combination, non-active ingredients medical preparations, medical preparations containing active ingredients, etc., can solve the problems of application obstacles, low stability, poor water solubility, etc. Good responsiveness, good selectivity, good effect
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Embodiment 1
[0035] The synthesis of embodiment 1Gal-GFLG-Sn38
[0036] (1) Synthesis of Alkyne-GFLG-OH
[0037] 1) Weigh 1000 mg of 2-chlorotrityl chloride resin (2-chlorotrityl chloride Resin) in a reaction vessel, add 5 mL of dry dichloromethane (CH 2 Cl 2 ) to swell the resin for 10 minutes, and vacuum the solvent to remove the resin with CH 2 Cl 2 and N,N-dimethylformamide (DMF) three times each. 2) N-(9-fluorenylmethoxycarbonyl)glycine (Fmoc-Gly-OH) was dissolved in 5mL DMF and added to the reaction tube, then N,N-diisopropylethylamine (DIEA) was added to shake and react for 12h. After washing, add 5 mL DMF, 200 μL MeOH, 400 μL DIEA, shake for 15 min, and repeat once. 3) Wash clean after the reaction, add 5mL DMF solution (containing 25% piperidine and 1% 1,5-diazabicyclo[5.4.0] (DBU)), shake for 15min, wash with DMF three times after suction filtration ,repeat. 4) Weigh N-fluorenylmethoxycarbonyl-[15N]leucine (Fmoc-Leu-OH), 1-hydroxybenzotriazole (HOBt) and N,N'-diisopropylcarb...
Embodiment 2
[0044] Synthesis of Example 2GalNAc-GFLG-Sn38
[0045] Steps (1) to (3) are the same as in Example 1.
[0046] (4) acetylgalactose-azide (GalNAc-N 3 ) (5.1 mg, 0.018 mmol) and Alkyne-GFLG-Sn38 (16.0 mg, 0.015 mmol) were dissolved in 500 μL DMSO, and sodium ascorbate (2.86 mg, 0.015 mmol) and CuSO were added in 125 μL distilled water 4 (3.61mg, 0.015mmol) was shaken until it turned turmeric, and the aqueous solution was transferred to a DMSO solution and stirred for 12 hours in the dark. After the solution was filtered, it was purified by preparative high-performance liquid chromatography, and freeze-dried to obtain a light yellow solid product. The retention time of GalNAc-GFLG-Sn38 analyzed by RP-HPLC was 26.3min. Molecular formula and molecular weight are C 69 h 87 N 11 o 20 + [M+Na] + 1412.6, the peak of 1412.6 was found by MALDI-TOF-MS analysis.
Embodiment 3
[0047] Synthesis of Example 3GlcNAc-GFLG-Sn38
[0048] Steps (1) to (3) are the same as in Example 1.
[0049] (4) GlcNAc-N 3 (5.1 mg, 0.018 mmol) and Alkyne-GFLG-Sn38 (16.0 mg, 0.015 mmol) were dissolved in 500 μL DMSO, and sodium ascorbate (2.86 mg, 0.015 mmol) and CuSO were added in 125 μL distilled water 4 (3.61mg, 0.015mmol) was shaken until it turned turmeric, and the aqueous solution was transferred to a DMSO solution and stirred for 12 hours in the dark. After the solution was filtered, it was purified by preparative high-performance liquid chromatography, and freeze-dried to obtain a light yellow solid product. The retention time of GlcNAc-GFLG-Sn38 analyzed by RP-HPLC was 26.3min. Molecular formula and molecular weight are C 69 h 87 N 11 o 20 + [M+Na] + 1412.6, the peak of 1412.6 was found by MALDI-TOF-MS analysis.
[0050] Above-mentioned synthesis process and each compound structural formula are as follows:
[0051]
PUM
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