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新型硫代缩氨基脲基锌(II)配合物。体外细胞毒性实验表明其对恶性黑色素瘤 A375 细胞的抑制作用强于顺铂,并与唾液酸酶抑制作用有关。

New thiosemicarbazone-based Zinc(II) complexes. In vitro cytotoxicity competing with cisplatin on malignant melanoma A375 cells and its relation to neuraminidase inhibition.

机构信息

Department of Chemistry, Inorganic Chemistry Section, Engineering Faculty, Istanbul University-Cerrahpaşa, 34320, Avcilar, Istanbul, Turkey.

Department of Physiology, Istanbul Medical Faculty, Istanbul University, 34390, Çapa, Istanbul, Turkey.

出版信息

Chem Biol Interact. 2022 Jan 5;351:109757. doi: 10.1016/j.cbi.2021.109757. Epub 2021 Nov 27.

DOI:10.1016/j.cbi.2021.109757
PMID:34848165
Abstract

New thiosemicarbazone-based zinc(II) complexes were synthesized to study their cytotoxicity on A375 malignant melanoma cells. The complexes containing salicylidene (Zn1a), 3-methoxy-salicylidene (Zn1b) or 4-methoxy-salicylidene (Zn1c) moiety were characterized by analytical and spectroscopic methods. Anticancer potential of the complexes was determined by MTT test and HUVEC endothelial cells line was used to comprehend the effect on normal cells. Zn1b with an IC of 13 μM was found to be highly cytotoxic against A375 cancer cells, more effective than cisplatin (IC: 37 μM). Zn1a and Zn1c did not have a negative effect on cell viability in the normal cells and gave the impression that they are more advantageous than cisplatin in this respect. Further, the ability of Zn1a-c to inhibit neuraminidase enzyme and its role in cytotoxicity was discussed. The test revealed that the Zn1b with 3-methoxy substituent exhibited higher inhibition activity against the neuraminidase than the Zn1a and Zn1c as analogical to the cytotoxicity results. In neuraminidase inhibition, IC values of Zn1b and Zn1c were 14 and 66 μM, respectively. These concentrations were very close to the cytotoxicity concentrations for Zn1b and Zn1c. The findings may indicate the role of neuraminidase enzyme inhibition in cell death for Zn1b and Zn1c.

摘要

新的席夫碱锌(II)配合物被合成以研究它们对 A375 恶性黑素瘤细胞的细胞毒性。含有水杨醛(Zn1a)、3-甲氧基水杨醛(Zn1b)或 4-甲氧基水杨醛(Zn1c)部分的配合物通过分析和光谱方法进行了表征。通过 MTT 试验测定了配合物的抗癌潜力,并使用 HUVEC 内皮细胞系来理解对正常细胞的影响。发现 Zn1b 对 A375 癌细胞具有高度的细胞毒性,IC 为 13 μM,比顺铂(IC:37 μM)更有效。Zn1a 和 Zn1c 对正常细胞的细胞活力没有负面影响,并且在这方面它们比顺铂更有优势。此外,还讨论了 Zn1a-c 抑制神经氨酸酶的能力及其在细胞毒性中的作用。实验表明,具有 3-甲氧基取代基的 Zn1b 对神经氨酸酶的抑制活性高于 Zn1a 和 Zn1c,这与细胞毒性结果一致。在神经氨酸酶抑制中,Zn1b 和 Zn1c 的 IC 值分别为 14 和 66 μM,分别。这些浓度与 Zn1b 和 Zn1c 的细胞毒性浓度非常接近。这些发现可能表明神经氨酸酶抑制在 Zn1b 和 Zn1c 的细胞死亡中起作用。

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