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Novel Anti-inflammatory and Analgesic Agents: Synthesis, Molecular Docking and In Vivo Studies

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 11007

Special Issue Editors


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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy
Interests: clinical biochemistry; inflammation; oxidative stress; neurodegeneration; natural compounds
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Special Issue Information

Dear Colleagues,

It is a pleasure for us to invite you to submit a review or a research article for publication in the Special Issue entitled “Novel Anti-inflammatory and Analgesic agents: Synthesis, Molecular Docking and In Vivo Studies” of the journal Molecules (MDPI).

Inflammation represents our body's first immune response to noxious stimuli. In the beginning, it is useful because it initiates healing processes. However, if the inflammatory stimulus persists, it can feed itself, enhancing inflammation and therefore harming the body. Inflammatory diseases are widespread all over the world, and inflammation remains a common and poorly controlled disease that can even lead to death, as in the case of allergies, autoimmune diseases, and rejection of transplanted organs. Chronic inflammation has been associated with a variety of diseases including cardiovascular disease, cancer, diabetes, arthritis, Alzheimer's disease, lung disease, and many others. Inflammatory diseases represent a common medical, social, and economic burden, and their pharmacotherapy is still an unsolved problem. Therefore, there is a great and urgent need to develop anti-inflammatory and analgesic agents with new mechanisms of action. Nonsteroidal anti-inflammatory drugs, glucocorticoids, and opioids were introduced into the clinic a long time ago, but in contrast to antihypertensive or anticancer drugs, the field of anti-inflammatory and analgesic agents has not changed much in the last few decades in terms of discovery of new mechanisms of action. Numerous biological drugs targeting several key molecules have represented a breakthrough in the treatment of certain autoimmune/inflammatory diseases such as rheumatoid arthritis and Crohn's disease. However, these products have numerous limitations such as high costs, inconvenient route of administration, which is often only parenteral, and long-term side effects that often restrain their administration and do not effectively reduce pain. In recent years, promising new approaches have been reported in different clinical phases of drug development focused on TRPV1/A1 channel antagonism (or agonism for desensitization), VCSC/VGCC blockade, inhibition of several enzymes (kinases, SSAO, MMP), cytokines/chemokines, transcription factors, NGF, and modulation of several G protein-coupled receptors (cannabinoids, purinoceptors, neuropeptides).

Therefore, this Special Issue will focus on the role and effectiveness of new anti-inflammatory and analgesic agents in promoting health and well-being. We welcome articles including results at the molecular level and those presenting data from in vivo experiments. In addition, review articles on therapeutic targets or biomarkers related to current anti-inflammatory and analgesic agents would complete this collection.

You may choose our Joint Special Issue in Chemistry.

Prof. Dr. Rosanna Di Paola
Dr. Rosalba Siracusa
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Inflammatory diseases
  • Autoimmune diseases
  • Analgesic agents
  • Anti-inflammatory effect
  • Mechanism of action
  • Molecules
  • Bioactive compounds
  • Natural agents
  • Functional food agents
  • Biochemistry

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Related Special Issue

Published Papers (4 papers)

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Research

16 pages, 1955 KiB  
Article
Design and Synthesis In Silico Drug-like Prediction and Pharmacological Evaluation of Cyclopolymethylenic Homologous of LASSBio-1514
by Lidia Moreira Lima, Tiago Fernandes da Silva, Carlos Eduardo da Silva Monteiro, Cristiane Aparecida-Silva, Walfrido Bispo Júnior, Aline Cavalcanti de Queiroz, Magna Suzana Alexandre-Moreira, Gisele Zapata-Sudo and Eliezer J. Barreiro
Molecules 2021, 26(16), 4828; https://doi.org/10.3390/molecules26164828 - 10 Aug 2021
Cited by 1 | Viewed by 2212
Abstract
Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation [...] Read more.
Acylhydrazones are still an important framework to the design of new bioactive compounds. As treatment of chronic pain represents a clinical challenge, we decided to modify the structure of LASSBio-1514 (1), previously described as anti-inflammatory and analgesic prototype. Applying the homologation as a strategy for molecular modification, we designed a series of cyclopentyl- (2ae), cyclobutyl- (3ae), and cyclopropylacylhydrazones (4ae) that were synthetized and evaluated in murine models of inflammation and pain. A comparison of their in silico physicochemical and drug-like profile was conducted, as well as their anti-inflammatory and analgesic effect. Compounds 4a (LASSBio-1755) and 4e (LASSBio-1757) displayed excellent in silico drug-like profiles and were identified as new analgesic lead-candidates in acute and chronic model of pain, through oral administration. Full article
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11 pages, 2022 KiB  
Article
Low Pre-Transplant Caveolin-1 Serum Concentrations Are Associated with Acute Cellular Tubulointerstitial Rejection in Kidney Transplantation
by Florian Emmerich, Stefan Zschiedrich, Christine Reichenbach-Braun, Caner Süsal, Susana Minguet, Marie-Christin Pauly and Maximilian Seidl
Molecules 2021, 26(9), 2648; https://doi.org/10.3390/molecules26092648 - 30 Apr 2021
Cited by 1 | Viewed by 1891
Abstract
Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. [...] Read more.
Acute and chronic transplant rejections due to alloreactivity are essential contributors to graft loss. However, the strength of alloreactivity is biased by non-immunological factors such as ischemia reperfusion injury (IRI). Accordingly, protection from IRI could be favorable in terms of limiting graft rejection. Caveolin-1 (Cav-1) is part of the cell membrane and an important regulator of intracellular signaling. Cav-1 has been demonstrated to limit IRI and to promote the survival of a variety of cell types including renal cells under stress conditions. Accordingly, Cav-1 could also play a role in limiting anti-graft immune responses. Here, we evaluated a possible association between pre-transplant serum concentrations of Cav-1 and the occurrence of rejection during follow-up in a pilot study. Therefore, Cav-1-serum concentrations were analyzed in 91 patients at the time of kidney transplantation and compared to the incidence of acute and chronic rejection. Higher Cav-1 levels were associated with lower occurrence of acute cellular tubulointerstitial rejection episodes. Full article
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17 pages, 3471 KiB  
Article
Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, Hemiscorpius lepturus
by Sedigheh Bagheri-Ziari, Delavar Shahbazzadeh, Soroush Sardari, Jean-Marc Sabatier and Kamran Pooshang Bagheri
Molecules 2021, 26(9), 2580; https://doi.org/10.3390/molecules26092580 - 28 Apr 2021
Cited by 15 | Viewed by 3340
Abstract
Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom [...] Read more.
Hemiscorpius lepturus scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in H. lepturus venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 μg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of H. lepturus venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action. Full article
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15 pages, 4986 KiB  
Article
Chrysophanol Attenuates Manifestations of Immune Bowel Diseases by Regulation of Colorectal Cells and T Cells Activation In Vivo
by Hyun-Su Lee and Gil-Saeng Jeong
Molecules 2021, 26(6), 1682; https://doi.org/10.3390/molecules26061682 - 17 Mar 2021
Cited by 3 | Viewed by 2614
Abstract
Inflammatory bowel disease (IBD) is an immune disorder that develops due to chronic inflammation in several cells. It is known that colorectal and T cells are mainly involved in the pathogenesis of IBD. Chrysophanol is an anthraquinone family member that possesses several bioactivities, [...] Read more.
Inflammatory bowel disease (IBD) is an immune disorder that develops due to chronic inflammation in several cells. It is known that colorectal and T cells are mainly involved in the pathogenesis of IBD. Chrysophanol is an anthraquinone family member that possesses several bioactivities, including anti-diabetic, anti-tumor, and inhibitory effects on T cell activation. However, it is unknown whether chrysophanol suppresses the activity of colorectal cells. In this study, we found that chrysophanol did not induce cytotoxicity in HT-29 colorectal cells. Pre-treatment with chrysophanol inhibited the mRNA levels of pro-inflammatory cytokines in tumor necrosis factor-α (TNF-α)-stimulated HT-29 cells. Western blot analysis revealed that pre-treatment with chrysophanol mitigates p65 translocation and the mitogen-activated protein kinase (MAPK) pathway in activated HT-29 cells. Results from the in vivo experiment confirmed that oral administration of chrysophanol protects mice from dextran sulfate sodium (DSS)-induced IBD. Chrysophanol administration attenuates the expression of pro-inflammatory cytokines in colon tissues of the DSS-induced IBD model. In addition, we found that oral administration of chrysophanol systemically decreased the expression of effector cytokines from mesenteric lymph nodes. Therefore, these data suggest that chrysophanol has a potent modulatory effect on colorectal cells as well as exhibiting a beneficial potential for curing IBD in vivo. Full article
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