Department of Science, Institute for Information Technologies, University of Kragujevac, Jovana Cvijića bb, 34000 Kragujevac, Serbia.
Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia.
Int J Mol Sci. 2022 Jan 1;23(1):490. doi: 10.3390/ijms23010490.
Free radicals often interact with vital proteins, violating their structure and inhibiting their activity. In previous studies, synthesis, characterisation, and the antioxidative properties of the five different coumarin derivatives have been investigated. In the tests of potential toxicity, all compounds exhibited low toxicity with significant antioxidative potential at the same time. In this paper, the radical scavenging activity of the abovementioned coumarin derivatives towards ten different radical species was investigated. It was found that all investigated compounds show good radical scavenging ability, with results that are in correlation with the results published in the previous study. Three additional mechanisms of radical scavenging activity were investigated. It was found that all three mechanisms are thermodynamically plausible and in competition. Interestingly, it was found that products of the Double Hydrogen Atom Transfer (DHAT) mechanism, a biradical species in triplet spin state, are in some cases more stable than singlet spin state analogues. This unexpected trend can be explained by spin delocalisation over the hydrazide bridge and phenolic part of the molecule with a low probability of spin pairing. Besides radical-scavenging activity, the pharmacokinetic and drug-likeness of the coumarin hybrids were investigated. It was found that they exhibit good membrane and skin permeability and potential interactions with P-450 enzymes. Furthermore, it was found that investigated compounds satisfy all criteria of the drug-likeness tests, suggesting they possess a good preference for being used as potential drugs.
自由基经常与重要的蛋白质相互作用，破坏其结构并抑制其活性。在以前的研究中，已经研究了五种不同香豆素衍生物的合成、表征和抗氧化性质。在潜在毒性测试中，所有化合物均表现出低毒性，同时具有显著的抗氧化潜力。在本文中，研究了上述香豆素衍生物对十种不同自由基的清除活性。结果表明，所有研究的化合物都具有良好的清除自由基能力，与以前研究的结果相关。还研究了三种额外的清除自由基活性机制。结果发现，所有三种机制在热力学上都是合理的，并且存在竞争。有趣的是，发现双氢原子转移（DHAT）机制的产物，三重态自旋状态的双自由基，在某些情况下比单重态类似物更稳定。这种出乎意料的趋势可以通过在分子的酰肼桥和酚部分上的自旋离域来解释，自旋配对的概率低。除了清除自由基活性外，还研究了香豆素杂合体的药代动力学和类药性。结果发现，它们表现出良好的膜和皮肤渗透性以及与 P-450 酶的潜在相互作用。此外，发现研究的化合物满足药物相似性测试的所有标准，表明它们具有作为潜在药物使用的良好偏好。
