Search Results (6)

Parkinson’s disease (PD) is a degenerative disease that affects approximately 6.1 million people and is primarily caused by the loss of dopaminergic neurons. Naphthoquinones have several biological activities explored in the literature, including neuroprotective effects. Therefore, this review shows an overview of naphthoquinones with neuroprotective effects, such as shikonin, plumbagin and vitamin K, that prevented oxidative stress, in addition to multiple mechanisms. Synthetic naphthoquinones with inhibitory activity on the P2X7 receptor were also found, leading to a neuroprotective effect on Neuro-2a cells. It was found that naphthazarin can act as inhibitors of the MAO-B enzyme. Vitamin K and synthetic naphthoquinones hybrids with tryptophan or dopamine showed inhibition of the aggregation of α-synuclein. Synthetic derivatives of juglone and naphthazarin were able to protect Neuro-2a cells against neurodegenerative effects of neurotoxins. In addition, routes for producing synthetic derivatives were also discussed. With the data presented, 1,4-naphthoquinones can be considered as a promising class in the treatment of PD and this review aims to assist the scientific community in the application of these compounds. The derivatives presented can also support further research that explores their structures as synthetic platforms, in addition to helping to understand the interaction of naphthoquinones with biological targets related to PD. Full article

This study investigated the effects of 1,4-naphthoquinone (NQ) and naphthazarin (5,8-dihydroxy-1,4-naphthoquinone, DHNQ) individually and in combination, applied at low concentrations (0.1, 1, and 10 nM), on growth, hydrogen peroxide (H₂O₂) production, catalase activity, and lipid peroxidation in maize seedlings. It was found that NQ at 0.1 and 1 nM and DHNQ at 0.1 nM significantly stimulated the fresh weight of the aboveground parts of the seedlings (APS), while the fresh weight of the underground parts of the seedlings (UPS) was enhanced only at 0.1 nM NQ. Interestingly, DHNQ at higher concentrations (1 and 10 nM) significantly diminished the fresh weight of the APS and UPS. When NQ and DHNQ were applied together, an increase in the fresh weight of the APS at all of the concentrations studied was observed. It was also found that NQ and DHNQ individually and in combination, at all concentrations studied, decreased the H₂O₂ production in the aboveground and underground parts of maize seedlings. The presence of the DHNQ at higher concentrations (1 and 10 nM) triggered an increase in the catalase (CAT) activity of the UPS and APS compared to the control. However, NQ added at 1 nM decreased the CAT activity of both the UPS and APS, while 10 nM increased the CAT activity of UPS. NQ and DHNQ applied together at 0.1 and 10 nM almost completely inhibited catalase activity in the UPS and APS. The data that were obtained for lipid peroxidation, measured as the malondialdehyde (MDA) concentration, indicated that NQ and DHNQ at all concentrations studied decreased the MDA content of the UPS, while both naphthoquinones increased it in APS. The data presented here are discussed taking into account the mechanisms via which naphthoquinones interact with biological systems. Full article

A series of naphthoquinones, namely, 1,4-naphthoquinone, menadione, plumbagin, juglone, naphthazarin, and lawsone, were reacted with N-acetyl-L-cysteine, and except for lawsone, which did not react, the related adducts were obtained. After the tuning of the solvent and reaction conditions, the reaction products were isolated as almost pure from the complex reaction mixture via simple filtration and were fully characterized. Therefore, the aim of this work was to evaluate whether the antitumor activity of new compounds of 1,4-naphthoquinone derivatives leads to an increase in ROS in tumor cell lines of cervical carcinoma (HeLa), neuroblastoma (SH-SY5Y), and osteosarcoma (SaOS2, U2OS) and in normal dermal fibroblast (HDFa). The MTT assay was used to assay cell viability, the DCF-DA fluorescent probe to evaluate ROS induction, and cell-cycle analysis to measure the antiproliferative effect. Compounds 8, 9, and 12 showed a certain degree of cytotoxicity towards all the malignant cell lines tested, while compound 11 showed biological activity at higher IC₅₀ values. Compounds 8 and 11 induced increases in ROS generation after 1 h of exposure, while after 48 h of treatment, only 8 induced an increase in ROS formation in HeLa cells. Cell-cycle analysis showed that compound 8 caused an increase in the number of G0/G1-phase cells in the HeLa experiment, while for the U2OS and SH-SY5Y cell lines, it led to an accumulation of S-phase cells. Therefore, these novel 1,4-naphthoquinone derivatives may be useful as antitumoral agents in the treatment of different cancers. Full article

Our long-term investigations have been devoted the characterization of intramolecular hydrogen bonds in cyclic compounds. Our previous work covers naphthazarin, the parent compound of two systems discussed in the current work: 2,3-dimethylnaphthazarin (1) and 2,3-dimethoxy-6-methylnaphthazarin (2). Intramolecular hydrogen bonds and substituent effects in these compounds were analyzed on the basis of Density Functional Theory (DFT), Møller–Plesset second-order perturbation theory (MP2), Coupled Clusters with Singles and Doubles (CCSD) and Car-Parrinello Molecular Dynamics (CPMD). The simulations were carried out in the gas and crystalline phases. The nuclear quantum effects were incorporated a posteriori using the snapshots taken from ab initio trajectories. Further, they were used to solve a vibrational Schrödinger equation. The proton reaction path was studied using B3LYP, $\omega$B97XD and PBE functionals with a 6-311++G(2d,2p) basis set. Two energy minima (deep and shallow) were found, indicating that the proton transfer phenomena could occur in the electronic ground state. Next, the electronic structure and topology were examined in the molecular and proton transferred (PT) forms. The Atoms In Molecules (AIM) theory was employed for this purpose. It was found that the hydrogen bond is stronger in the proton transferred (PT) forms. In order to estimate the dimers’ stabilization and forces responsible for it, the Symmetry-Adapted Perturbation Theory (SAPT) was applied. The energy decomposition revealed that dispersion is the primary factor stabilizing the dimeric forms and crystal structure of both compounds. The CPMD results showed that the proton transfer phenomena occurred in both studied compounds, as well as in both phases. In the case of compound 2, the proton transfer events are more frequent in the solid state, indicating an influence of the environmental effects on the bridged proton dynamics. Finally, the vibrational signatures were computed for both compounds using the CPMD trajectories. The Fourier transformation of the autocorrelation function of atomic velocity was applied to obtain the power spectra. The IR spectra show very broad absorption regions between 700 cm${}^{-1}$–1700 cm${}^{-1}$ and 2300 cm${}^{-1}$–3400 cm${}^{-1}$ in the gas phase and 600 cm${}^{-1}$–1800 cm${}^{-1}$ and 2200 cm${}^{-1}$–3400 cm${}^{-1}$ in the solid state for compound 1. The absorption regions for compound 2 were found as follows: 700 cm${}^{-1}$–1700 cm${}^{-1}$ and 2300 cm${}^{-1}$–3300 cm${}^{-1}$ for the gas phase and one broad absorption region in the solid state between 700 cm${}^{-1}$ and 3100 cm${}^{-1}$. The obtained spectroscopic features confirmed a strong mobility of the bridged protons. The inclusion of nuclear quantum effects showed a stronger delocalization of the bridged protons. Full article

Non-covalent interactions responsible for molecular features and self-assembly in Naphthazarin C polymorph were investigated on the basis of diverse theoretical approaches: Density Functional Theory (DFT), Diffusion Quantum Monte Carlo (DQMC), Symmetry-Adapted Perturbation Theory (SAPT) and Car-Parrinello Molecular Dynamics (CPMD). The proton reaction paths in the intramolecular hydrogen bridges were studied. Two potential energy minima were found indicating that the proton transfer phenomena occur in the electronic ground state. Diffusion Quantum Monte Carlo (DQMC) and other levels of theory including Coupled Cluster (CC) employment enabled an accurate inspection of Potential Energy Surface (PES) and revealed the energy barrier for the proton transfer. The structure and reactivity evolution associated with the proton transfer were investigated using Harmonic Oscillator Model of Aromaticity - HOMA index, Fukui functions and Atoms In Molecules (AIM) theory. The energy partitioning in the studied dimers was carried out based on Symmetry-Adapted Perturbation Theory (SAPT) indicating that dispersive forces are dominant in the structure stabilization. The CPMD simulations were performed at 60 K and 300 K in vacuo and in the crystalline phase. The temperature influence on the bridged protons dynamics was studied and showed that the proton transfer phenomena were not observed at 60 K, but the frequent events were noticed at 300 K in both studied phases. The spectroscopic signatures derived from the CPMD were computed using Fourier transformation of autocorrelation function of atomic velocity for the whole molecule and bridged protons. The computed gas-phase IR spectra showed two regions with OH absorption that covers frequencies from 2500 cm${}^{-1}$ to 2800 cm${}^{-1}$ at 60 K and from 2350 cm${}^{-1}$ to 3250 cm${}^{-1}$ at 300 K for both bridged protons. In comparison, the solid state computed IR spectra revealed the environmental influence on the vibrational features. For each of them absorption regions were found between 2700–3100 cm${}^{-1}$ and 2400–2850 cm${}^{-1}$ at 60 K and 2300–3300 cm${}^{-1}$ and 2300–3200 cm${}^{-1}$ at 300 K respectively. Therefore, the CPMD study results indicated that there is a cooperation of intramolecular hydrogen bonds in Naphthazarin molecule. Full article

Naphthoquinones, plants secondary metabolites are known for their antibacterial, antifungal, anti-inflammatory, anti-cancer and anti-parasitic properties. The biological activity of naphthoquinones is connected with their ability to generate reactive oxygen species and to modify biological molecules at their nucleophilic sites. In our research, the effect of naphthazarin (DHNQ) combined with 2-hydroxy-1,4-naphthoquinone (NQ-2-OH) or 1,4-naphthoquinone (1,4-NQ) on the elongation growth, pH changes of the incubation medium, oxidative stress and redox activity of maize coleoptile cells were investigated. This paper describes experiments performed with maize (Zea mays L.) coleoptile segments, which is a classical model system to study plant cell elongation growth. The data presented clearly demonstrate that lawsone and 1,4-naphthoquinone combined with naphthazarin, at low concentrations (1 and 10 nM), reduced the endogenous and IAA-induced (Indole-3-Acetic Acid) elongation growth of maize coleoptile segments. Those changes in growth correlated with the proton concentration in the incubation medium, which suggests that the changes in the growth of maize coleoptile segments observed in the presence of naphthoquinones are mediated through the activity of PM H⁺-ATPase. The presence of naphthoquinones induced oxidative stress in the maize coleoptile tissue by producing hydrogen peroxide and causing changes in the redox activity. Moreover, the incubation of maize segments with both naphthoquinones combined with naphthazarin resulted in lipid peroxidation and membrane damage. The regulation of PM H⁺-ATPase activity, especially its inhibition, may result from two major types of reaction: first, a direct interaction between an enzyme and naphthoquinone, which leads to the covalent modification of the protein thiols and the generation of thioethers, which have been found to alter the activity of the PM H⁺-ATPases; second, naphthoquinones induce reactive oxygen species (ROS) production, which inhibits PM H⁺-ATPases by increasing cytosolic Ca²⁺. This harmful effect was stronger when naphthazarin and 1,4-naphthoquinone were added together. Taking these results into account, it can be suggested that by combining naphthoquinones in small quantities, an alternative to synthetic pesticides could be developed. Full article