Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry RAS, Chernogolovka, Russian Federation.
Silesian University of Technology, Gliwice, Poland.
J Biol Phys. 2023 Jun;49(2):269-282. doi: 10.1007/s10867-023-09631-5. Epub 2023 Mar 18.
Water-soluble fullerene derivatives are good candidates for various biological applications such as anticancer or antimicrobial therapy, cytoprotection, enzyme inhibition, and many others. Their toxicity, both in tissue culture and in vivo, is a critical characteristic for the development and restriction of these applications. The effects of six water-soluble cationic and anionic polysubstituted fullerene derivatives on cytochrome c oxidase activity in rat brain mitochondria and the possibility of cytochrome c binding were studied. We found that the ability of these fullerene derivatives to bind with cytochrome c oxidase and charged molecules like eosin Y strongly depends on their electrostatic charge. As was shown, the cationic fullerene derivative inhibits cytochrome c oxidase that has the overall negative electrostatic potential completely, unlike anionic derivatives. Thus, it confirms the essential role of electrostatic interactions in the interaction of fullerene derivatives with the active site of enzymes. The results explore how cationic fullerene derivatives play a role in mitochondrial dysfunction, oxidative stress, and cytotoxicity.
水溶性富勒烯衍生物是各种生物应用的候选者，如抗癌或抗菌治疗、细胞保护、酶抑制等。它们在组织培养和体内的毒性是这些应用的发展和限制的关键特征。本研究考察了六种水溶性阳离子和阴离子多取代富勒烯衍生物对大鼠脑线粒体细胞色素 c 氧化酶活性的影响及其与细胞色素 c 结合的可能性。我们发现，这些富勒烯衍生物与细胞色素 c 氧化酶和像曙红 Y 这样的带电分子结合的能力强烈依赖于它们的静电电荷。结果表明，阳离子富勒烯衍生物完全抑制具有整体负静电势的细胞色素 c 氧化酶，而阴离子衍生物则不会。因此，这证实了静电相互作用在富勒烯衍生物与酶的活性位点相互作用中的重要作用。该结果探讨了阳离子富勒烯衍生物如何在线粒体功能障碍、氧化应激和细胞毒性中发挥作用。
