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氧杂蒽和硫杂蒽衍生物作为抗氧化剂、抗癌剂和COX抑制剂的生物学评价

Biological Evaluation of Xanthene and Thioxanthene Derivatives as Antioxidant, Anticancer, and COX Inhibitors.

作者信息

Abualhasan Murad, Hawash Mohammed, Aqel Samah, Al-Masri Motasem, Mousa Ahmed, Issa Linda

机构信息

Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, P400 Nablus, Palestine.

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, P.O. Box 7, P400 Nablus, Palestine.

出版信息

ACS Omega. 2023 Oct 3;8(41):38597-38606. doi: 10.1021/acsomega.3c05695. eCollection 2023 Oct 17.

Abstract

Xanthene and thioxanthene analogues have been investigated for their potential as anticancer and anti-inflammatory agents. Additionally, cysteine analogues have been found to possess antioxidant, anti-inflammatory, and anticancer activities due to their role in cellular redox balance, scavenging of free radicals, and involvement in nucleophilic reactions and enzyme binding sites. In this study, we synthesized a library of tertiary alcohols derived from xanthene and thioxanthene, and further, some of these compounds were coupled with cysteine. The objective of this research was to explore the potential anticancer, antioxidant, and anti-inflammatory activities of the synthesized compounds. The synthesized compounds were subjected to test for anticancer, antioxidant, and anti-inflammatory activities. Results indicated that compound exhibited excellent inhibition activity (IC = 9.6 ± 1.1 nM) against colon cancer cells (Caco-2), while compound showed good inhibition activity (IC = 161.3 ± 41 nM) against hepatocellular carcinoma (Hep G2) cells. Compound demonstrated potent antioxidant inhibition activity (IC = 15.44 ± 6 nM), and compound exhibited potent anti-inflammatory activity with cyclooxygenase-2 (COX-2) inhibition IC (4.37 ± 0.78 nM) and high selectivity for COX-2 (3.83). In conclusion, certain synthesized compounds displayed promising anticancer activity and anti-inflammatory effects. Nevertheless, additional research is necessary to create more analogues, develop a more distinct comprehension of the structure-activity relationship (SAR), and perform in vivo experiments to evaluate the pharmacokinetic and pharmacodynamic characteristics of the compounds under examination. Such research may pave the way for the development of novel therapeutic agents with potential applications in cancer and inflammatory diseases.

摘要

呫吨和噻吨类似物已被研究其作为抗癌和抗炎剂的潜力。此外,半胱氨酸类似物因其在细胞氧化还原平衡、自由基清除以及参与亲核反应和酶结合位点方面的作用而被发现具有抗氧化、抗炎和抗癌活性。在本研究中,我们合成了一系列源自呫吨和噻吨的叔醇,并且进一步将其中一些化合物与半胱氨酸偶联。本研究的目的是探索合成化合物潜在的抗癌、抗氧化和抗炎活性。对合成化合物进行了抗癌、抗氧化和抗炎活性测试。结果表明,化合物对结肠癌细胞(Caco-2)表现出优异的抑制活性(IC = 9.6 ± 1.1 nM),而化合物对肝癌细胞(Hep G2)表现出良好的抑制活性(IC = 161.3 ± 41 nM)。化合物表现出强效的抗氧化抑制活性(IC = 15.44 ± 6 nM),并且化合物对环氧合酶-2(COX-2)具有强效抗炎活性,其抑制IC为(4.37 ± 0.78 nM),对COX-2具有高选择性(3.83)。总之,某些合成化合物显示出有前景的抗癌活性和抗炎作用。然而,需要进一步的研究来制备更多类似物,更深入地理解构效关系(SAR),并进行体内实验以评估所研究化合物的药代动力学和药效学特征。此类研究可能为开发在癌症和炎症性疾病中具有潜在应用的新型治疗药物铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5f61/10586285/b63e010042ea/ao3c05695_0006.jpg

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