十字孢碱磺酰化产物合成及其细胞毒活性研究

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中图分类号：R978.1 文献标志码：A

文章编号：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

十字孢碱最初被发现于1977年，由Omura等[1]在放线菌Streptomyces staurosporeus ATCC55006的培养液中分离而得，并命名为AM-2282。（剩余23361字）