Department of Chemistry, College of Sciences, Taif University, Taif, Saudi Arabia.
Department of Biology, College of Science, University of Jeddah, Jeddah, Saudi Arabia.
PeerJ. 2024 Jan 2;12:e15638. doi: 10.7717/peerj.15638. eCollection 2024.
A novel Artemisinin/Quercetin/Zinc (Art/Q/Zn) mixed ligand complex was synthesized, tested for its antiviral activity against coronavirus (SARS-CoV-2), and investigated for its effect against toxicity and oxidative stress induced by acrylamide (Acy), which develops upon cooking starchy foods at high temperatures. The synthesized complex was chemically characterized by performing elemental analysis, conductance measurements, FT-IR, UV, magnetic measurements, and XRD. The morphological surface of the complex Art/Q/Zn was investigated using scanning and transmission electron microscopy (SEM and TEM) and energy dispersive X-ray analysis (XRD). The antiviral activity of the complex Art/Q/Zn against SARS-CoV-2 and its activity against Acy-induced toxicity in hepatic and pulmonary tissues were analyzed. An experimental model was used to evaluate the beneficial effects of the novel Art/Q/Zn novel complex on lung and liver toxicities of Acy. Forty male rats were randomly divided into four groups: control, Acy (500 mg/Kg), Art/Q/Zn (30 mg/kg), and a combination of Acy and Art/Q/Zn. The complex was orally administered for 30 days. Hepatic function and inflammation marker (CRP), tumor necrosis factor, interleukin-6 (IL-6), antioxidant enzyme (CAT, SOD, and GPx), marker of oxidative stress (MDA), and blood pressure levels were investigated. Histological and ultrastructure alterations and caspase-3 variations (immunological marker) were also investigated. FT-IR spectra revealed that Zn (II) is able to chelate through C=O and C-OH (Ring II) which are the carbonyl oxygen atoms of the quercetin ligand and carbonyl oxygen atom C=O of the Art ligand, forming Art/Q/Zn complex with the chemical formula [Zn(Q)(Art)(Cl)(HO)]⋅3HO. The novel complex exhibited a potent anti-SARS-CoV-2 activity even at a low concentration (IC = 10.14 µg/ml) and was not cytotoxic to the cellular host (CC = 208.5 µg/ml). Art/Q/Zn may inhibit the viral replication and binding to the angiotensin-converting enzyme-2 (ACE2) receptor and the main protease inhibitor (M), thereby inhibiting the activity of SARS-CoV-2 and this proved by the molecular dynamics simulation. It alleviated Acy hepatic and pulmonary toxicity by improving all biochemical markers. Therefore, it can be concluded that the novel formula Art/Q/Zn complex is an effective antioxidant agent against the oxidative stress series, and it has high inhibitory effect against SARS-CoV-2.
一种新型青蒿素/槲皮素/锌(Art/Q/Zn)混合配体配合物被合成,并测试其对冠状病毒(SARS-CoV-2)的抗病毒活性,同时研究其对丙烯酰胺(Acy)诱导的毒性和氧化应激的影响,丙烯酰胺在高温烹饪淀粉类食物时会产生。通过进行元素分析、电导率测量、FT-IR、UV、磁测量和 XRD,对合成的配合物进行了化学表征。通过扫描电子显微镜(SEM)和透射电子显微镜(TEM)以及能量色散 X 射线分析(EDX)研究了配合物 Art/Q/Zn 的表面形态。分析了新型 Art/Q/Zn 配合物对 SARS-CoV-2 的抗病毒活性及其对肝和肺组织中 Acy 诱导毒性的作用。使用实验模型评估新型 Art/Q/Zn 配合物对 Acy 肺和肝毒性的有益作用。将 40 只雄性大鼠随机分为四组:对照组、Acy(500mg/kg)、Art/Q/Zn(30mg/kg)和 Acy 和 Art/Q/Zn 的组合。配合物经口给药 30 天。研究了肝功能和炎症标志物(CRP)、肿瘤坏死因子、白细胞介素-6(IL-6)、抗氧化酶(CAT、SOD 和 GPx)、氧化应激标志物(MDA)和血压水平。还研究了组织学和超微结构改变以及 caspase-3 变化(免疫标志物)。FT-IR 光谱表明,Zn(II)能够通过与槲皮素配体的 C=O 和 C-OH(环 II)以及青蒿素配体的 C=O 羰基氧原子螯合,形成化学式为[Zn(Q)(Art)(Cl)(HO)]⋅3HO 的 Art/Q/Zn 配合物。新型配合物表现出强大的抗 SARS-CoV-2 活性,即使在低浓度(IC=10.14μg/ml)下也是如此,并且对细胞宿主没有细胞毒性(CC=208.5μg/ml)。Art/Q/Zn 可能通过抑制病毒复制和与血管紧张素转化酶-2(ACE2)受体和主要蛋白酶抑制剂(M)的结合,从而抑制 SARS-CoV-2 的活性,这一点通过分子动力学模拟得到了证明。它通过改善所有生化标志物来减轻 Acy 的肝和肺毒性。因此,可以得出结论,新型配方 Art/Q/Zn 配合物是一种有效的抗氧化剂,可对抗氧化应激系列,对 SARS-CoV-2 具有高抑制作用。