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Effect of organo-selenium anticancer drugs on nitrite induced methemoglobinemia: A spectroscopic study
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy ( IF 4.3 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.saa.2020.118946
Debashree Das , Kamalika Sen

Selenium containing drugs like selenomethionine, selenocystine, selenourea and methylseleninic acid are reported to exhibit potential anticancer effect. However, these anticancer drugs may exert adverse effects when used over a prolonged period. Little is known about the interaction of these selenium containing drugs with the vital erythroid protein hemoglobin. In this work a comparative study of the interaction of organo-selenium drugs with hemoglobin and heme moiety has been performed using different spectroscopic techniques to find out their role on drug induced methemoglobinemia. We found that though these selenium containing drugs have similar binding affinity towards hemoglobin, they have differential interactions with the heme group. Isothermal calorimetric titration study showed that selenourea has the lowest binding affinity (Kd 19.28 μM) towards HbA as compared to other drugs, selenomethionine, selenocystine and methylseleninic acid (Kd 7.69 μM, 4.88 μM and 10.5 μM at 37 °C respectively). This result is also supported by the molecular docking study. Methylseleninic acid was found to have detrimental effects on nitrite induced methemoglobinemia, a hematological disorder caused due to excessive conversion of Fe2+ to Fe3+ in hemoglobin. Hence the results of the study would help to develop a better insight on the mechanism of action and anticipate the toxicity of these drugs which require further optimization before their actual use in the treatment of cancer.



中文翻译:

有机硒抗癌药对亚硝酸盐诱导的高铁血红蛋白血症的影响:光谱研究

据报道,含硒药物如硒代蛋氨酸,硒代半胱氨酸,硒硒和甲基硒酸具有潜在的抗癌作用。但是,长时间使用这些抗癌药可能会产生不良反应。这些含硒药物与重要的类红细胞蛋白血红蛋白之间的相互作用鲜为人知。在这项工作中,已经使用不同的光谱技术对有机硒药物与血红蛋白和血红素部分的相互作用进行了比较研究,以发现它们在药物诱导的高铁血红蛋白血症中的作用。我们发现尽管这些含硒药物对血红蛋白具有相似的结合亲和力,但它们与血红素基团具有不同的相互作用。等温滴定研究表明硒硒具有最低的结合亲和力(Kd 19.28μM)朝向的HbA相比于其他药物,硒代蛋氨酸,硒代胱氨酸和methylseleninic酸(K d 7.69μM,4.88μM和10.5μM在37℃下分别地)。分子对接研究也支持这一结果。发现甲基硒酸对亚硝酸盐诱导的高铁血红蛋白血症具有有害作用,高铁血红蛋白血症是由于血红蛋白中Fe 2+过度转化为Fe 3+而引起的血液病。因此,研究结果将有助于更好地了解作用机理,并预测这些药物的毒性,这些药物在实际用于癌症治疗之前需要进一步优化。

更新日期:2020-09-23
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