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Effect of organo-selenium anticancer drugs on nitrite induced methemoglobinemia: A spectroscopic study
D. Das,
Published in Elsevier B.V.
PMID: 32979808
Volume: 245
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. © 2020 Elsevier B.V.
About the journal
JournalData powered by TypesetSpectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy
PublisherData powered by TypesetElsevier B.V.