十字孢堿磺酰化產(chǎn)物合成及其細(xì)胞毒活性研究
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中圖分類號：R978.1 文獻(xiàn)標(biāo)志碼：A
文章編號：1001-8689（2025）04-0383-11
Study on the synthesis and cytotoxic activity of sulfonated staurosporine
Zhao Linchun1.2，Li Gang1.2， Xu Yanchaol， Zhu Weiming3，and Wang Liping1，2 （1 State KeyLaborataoryofFunctionsandAplicationsofMedicialPlants，GuizouMedicalUniversityGuiyang55o4；atural Products Research Center of Guizhou Province， Guiyang 55o014; 3 School of Medicine and Pharmacy， Ocean University ofChina，Qingdao 266003）
AbstractObjective To modify the structure of staurosporine from actinomycetes to enrich the diversity of its chemical structure and to find the antitumor lead compound with selective inhibition activity.MethodsThe sulfonated derivatives of staurosporine were prepared by the reaction of staurosporine with sulfonyl chloride at 3'- N.The target compounds were separated and purified by chromatography.The structures of the compounds were determined by mass spectrometry （MS）， high-resolution mass spectrometry （HRESIMS） and nuclear magnetic resonance （ 1H NMR and 13C NMR）. The cytotoxic activity of the derivatives was evaluated by the CCK-8 method. ResultsFourteen sulfonated staurosporines were synthesized，of which 13compounds （1 and 3＼～14） were first synthesized.Allof the compounds showed inhibitory activityon the human acute myeloid leukemia cell lineMV4-11， and mostof thecompounds showed good inhibitoryactivityon thehumanacute myeloid leukemiacelline HL-60， among which compounds 5 and 12 showed selective inhibitory activity on HL-60 tumor cels. The IC50 values were 0.86 and ， respectively， and the selection index SI （ IC50 of normal cell/IC50 of tumor cell） were 7 and 8， respectively， which were superior to the positive drug PKC-412 （ IC50 of 8.92μmol/L ， SI of 1）. Most of the compounds do not produce cytotoxic activity against the human normal liver cell line L-O2. ConclusionThe sulfonated staurosporine derivativesshowed good inhibitoryactivityagainst MV4-11 and HL-60 tumorcell lines.This indicated that thesecompounds hadtheadvantages ofhigh effciencyand low toxicity，hadthe valueoffurtherresearch，and could be expected to be developed as new anti-tumor drugs.
Key wordsStaurosporine; Alkaloid; Sulfonylation; Cytotoxic activity
十字孢堿最初被發(fā)現(xiàn)于1977年，由Omura等[1]在放線菌Streptomyces staurosporeus ATCC55006的培養(yǎng)液中分離而得，并命名為AM-2282。（剩余23361字）