Synthesis and Biological Activities of Chemical Drugs for the Treatment of Rheumatoid Arthritis

Zhou, Shiyang; Zou, Huiying; Chen, Guang‐Ying; Huang, Gangliang

doi:10.1007/s41061-019-0252-5

Cited by 38 publications

(27 citation statements)

References 63 publications

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“…At present, most drugs for rheumatoid arthritis have little effect on the pathological process of RA. Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease [1,2].…”

Section: Introductionmentioning

confidence: 99%

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Wang

et al. 2020

Neural Plasticity

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At present, most of the drugs have little effect on the pathological process of rheumatoid arthritis (RA). Analgesia is an important measure in the treatment of RA and is also one of the criteria to determine the therapeutic effects of the disease. Some studies have found that crocin, a kind of Chinese medicine, can effectively alleviate pain sensitization in pain model rats, but the mechanism is not clear. Emerging evidence indicates that crocin may inhibit the metastasis of lung and liver cancer cells from the breast by inhibiting Wnt/β-catenin and the Wnt signaling pathway is closely related to RA. Wnt5a belongs to the Wnt protein family and was previously thought to be involved only in nonclassical Wnt signaling pathways. Recent studies have shown that Wnt5a has both stimulatory and inhibitory effects on the classical Wnt signaling pathway, and so, Wnt5a has attracted increasing attention. This study demonstrated that crocin significantly increased the mechanical thresholds of adjuvant-induced arthritis (AIA) rats, suggesting that crocin can alleviate neuropathic pain. Crocin significantly decreased the levels of pain-related factors and glial activation. Foxy5, activator of Wnt5a, inhibited the above effects of crocin in AIA rats. In addition, intrathecal injection of a Wnt5a inhibitor significantly decreased hyperalgesia in AIA rats. This research shows that crocin may alleviate neuropathic pain in AIA rats by inhibiting the expression of pain-related molecules through the Wnt5a/β-catenin pathway, elucidating the mechanism by which crocin relieves neuropathic pain and provides a new way of thinking for the treatment of AIA pain.

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Section: Introductionmentioning

confidence: 99%

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Wang

et al. 2020

Neural Plasticity

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“…However, any joint can be affected and severe non-joint systemic symptoms may occur [ 5 ]. Nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, disease-modifying anti-rheumatic drugs (DMARDs), and biologicals are used for the long-term treatment of RA [ 6 ] but their application does not usually lead to complete remission. In addition, the sustained administration of current anti-rheumatic agents might induce severe side effects, e.g., gastric ulceration, osteoporosis, or hematotoxicity.…”

Section: Introductionmentioning

confidence: 99%

Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation

et al. 2020

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Polymer-drug conjugates have several advantages in controlled drug delivery to inflammation as they can accumulate and release the drug in inflamed tissues or cells, which could circumvent the shortcomings of current therapy. To improve the therapeutic potential of polymer-drug conjugates in joint inflammation, we synthesized polymer conjugates based on N-(2-hydroxypropyl) methacrylamide) copolymers labeled with a near-infrared fluorescent dye and covalently linked to the anti-inflammatory drug dexamethasone (DEX). The drug was bound to the polymer via a spacer enabling pH-sensitive drug release in conditions mimicking the environment inside inflammation-related cells. An in vivo murine model of adjuvant-induced arthritis was used to confirm the accumulation of polymer conjugates in arthritic joints, which occurred rapidly after conjugate application and remained until the end of the experiment. Several tested dosage schemes of polymer DEX-OPB conjugate showed superior anti-inflammatory efficacy. The highest therapeutic effect was obtained by repeated i.p. application of polymer conjugate (3 × 1 mg/kg of DEX eq.), which led to a reduction in the severity of inflammation in the ankle by more than 90%, compared to 40% in mice treated with free DEX.

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“…There has been a general trend toward more information rich 3D specific or quantum chemical descriptors in QSAR modeling studies associated with ligand bioactivity. This includes the incorporation of dynamical effects via descriptors derived from MD simulations and interaction energies and conformational energies via quantum mechanics (QM) . and chemical reactivity .…”

Section: Introductionmentioning

confidence: 99%

“…This includes the incorporation of dynamical effects via descriptors derived from MD simulations [34][35][36] and interaction energies and conformational energies via quantum mechanics (QM). [37][38][39][40] and chemical reactivity. [41,42] Indeed, these trends toward more information-rich descriptors have been observed in studies related to skin sensitization prediction given that chemical reactivity can be encoded much effectively with quantum chemical-derived descriptors than those that are empirical derived.…”

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confidence: 99%

Theoretical studies to estimate the skin sensitization potential of chemicals of the Schiff base domain

Gleeson

2020

Int J of Quantum Chemistry

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Skin sensitization occurs when an exogenous chemical substance forms a covalent adduct with a dermal protein electrophile or nucleophile. This instigates an immune response which leads to inflammation. The local lymph node assay is an in vivo model used in the assessment of relative skin sensitizing potency of chemicals. The method is time consuming and expensive, as well as poses ethical questions given that a number of mice must be sacrificed for each compound assessed. In this work, we investigate the use of an inexpensive, rapid, and ethical method to predict the skin sensitization potential of Schiff base chemicals. We employ quantum chemical methods to rationalize the sensitization potential of 22 compounds with a diverse range of activities. To this end, we have evaluated the mechanistic profile associated with this type of reaction using gas-phase models. We subsequently use the predicted rate determining barriers and key physico-chemical parameters (such as logP) to establish stucture activity relationship (SAR) guidelines to predict the skin sensitization potential for new chemicals. We find that the predicted rate determining barriers for aldehydes, ketone, and 1,2 and 1,3 diones generally decrease in the given order, which concurs with the overall trends in sensitization. We find that lipophilicity also plays a role, with those chemicals displaying both low barriers to reaction, and lower lipophilicity (ie, diones), being more likely to display undesirable skin sensitization effects. These findings are in line with experiment-based observations in the literature and point to the value 3D quantum chemical calculations could have if combined with other orthogonal approaches to estimate skin sensitization potential of chemicals. K E Y W O R D S DFT, EC3, QM calculation, Schiff base, LLNA, skin sensitization

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Synthesis and Biological Activities of Chemical Drugs for the Treatment of Rheumatoid Arthritis

Cited by 38 publications

References 63 publications

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Crocin Alleviates Pain Hyperalgesia in AIA Rats by Inhibiting the Spinal Wnt5a/β-Catenin Signaling Pathway and Glial Activation

Polymer Nanomedicines with Ph-Sensitive Release of Dexamethasone for the Localized Treatment of Inflammation

Theoretical studies to estimate the skin sensitization potential of chemicals of the Schiff base domain

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