| 1. |
- El-Seedi, Hesham R., et al.
(författare)
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Naturally Occurring Xanthones; Biological Activities, Chemical Profiles and In Silico Drug Discovery
- 2024
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 31:1, s. 62-101
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Forskningsöversikt (refereegranskat)abstract
- Xanthones are widely distributed polyphenols, present commonly in higher plants; Garcinia, Calophyllum, Hypericum, Platonia, Mangifera, Gentiana and Swertia. Xanthone tricyclic scaffold is able to interact with different biological targets, showing antibacterial and cytotoxic effects, as well as potent effects against osteoarthritis, malaria, and cardiovascular diseases. Thus, in this article we focused on pharmacological effects, applications and preclinical studies with the recent updates of xanthon & PRIME;s isolated compounds from 2017-2020. We found that only a-mangostin, gambogic acid, and mangiferin, have been subjected to preclinical studies with particular emphasis on the development of anticancer, diabetes, antimicrobial and hepatoprotective therapeutics. Molecular docking calculations were performed to predict the binding affinities of xanthone-derived compounds against SARS-CoV-2 M-pro. According to the results, cratoxanthone E and morellic acid demonstrated promising binding affinities towards SARS-CoV-2 M-pro with docking scores of -11.2 and -11.0 kcal/mol, respectively. Binding features manifested the capability of cratoxanthone E and morellic acid to exhibit nine and five hydrogen bonds, respectively, with the key amino acids of the M-pro active site. In conclusion, cratoxanthone E and morellic acid are promising anti-COVID-19 drug candidates that warrant further detailed in vivo experimental estimation and clinical assessment.
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| 2. |
- Lehtimäki, Lauri, et al.
(författare)
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Clinical Values of Nitric Oxide Parameters from the Respiratory System
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:42, s. 7189-7199
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Fractional exhaled nitric oxide (FENO) concentration reliably reflects central airway inflammation, but it is not sensitive to changes in the NO dynamics in the lung periphery. By measuring FENO at several different flow rates one can estimate alveolar NO concentration (CANO), bronchial NO flux (JawNO), bronchial wall NO concentration (CawNO) and the bronchial diffusivity of NO (DawNO).OBJECTIVE: We aimed to describe the current knowledge and clinical relevance of NO parameters in different pulmonary diseases.METHODS: We conducted a systematic literature search to identify publications reporting NO parameters in subjects with pulmonary or systemic diseases affecting the respiratory tract. A narrative review was created for those with clinical relevance.RESULTS: Estimation of pulmonary NO parameters allows for differentiation between central and peripheral inflammation and a more precise analysis of central airway NO output. CANO seems to be a promising marker of parenchymal inflammation in interstitial lung diseases and also a marker of tissue damage and altered gas diffusion in chronic obstructive pulmonary disease and systemic diseases affecting the lung. In asthma, CANO can detect small airway involvement left undetected by ordinary FENO measurement. Additionally, CawNO and DawNO can be used in asthma to assess if FENO is increased due to enhanced inflammatory activity (increased CawNO) or tissue changes related to bronchial remodelling (altered DawNO).CONCLUSION: NO parameters may be useful for diagnosis, prediction of disease progression and prediction of treatment responses in different parenchymal lung and airway diseases. Formal trials to test the added clinical value of NO parameters are needed.
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| 3. |
- Liu, Shan, et al.
(författare)
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Recent Progress on the Synthesis and Biomedical Properties of Natural Biopolymer Composites
- 2021
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers. - 0929-8673 .- 1875-533X. ; 28:40, s. 8243-8266
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Forskningsöversikt (refereegranskat)abstract
- Background: Natural biopolymers have drawn extensive attention because of their great biocompatibility, biodegradability, renewability, and the availability of various reactive functional groups for modifying and introducing novel components. In the last few years, numerous natural biopolymer composites have been exploited to improve their physical and chemical properties and add new functionalities.Methods: Herein, we summarize the current progress in three common classes of natural biopolymer-based composites, including alginate, chitosan, and gelatin.Results: The morphology characteristics, preparation methods, and unique functionalities of these biopolymer composites are also analyzed and discussed.Conclusion: Finally, the article offers an overview of recent progress in the main biomedical applications such as tissue engineering, wound-healing, and drug delivery, which inspires further progress in biopolymer composites with tailored mechanical property and stable characteristics for pharmaceutical and biomedical applications.
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| 4. |
- Mitran, Bogdan, et al.
(författare)
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Radiolabeled GRPR Antagonists for Imaging of Disseminated Prostate Cancer : Influence of Labeling Chemistry on Targeting Properties
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:41, s. 7090-7111
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Radionuclide molecular imaging of gastrin-releasing peptide receptor (GRPR) expression promises unparalleled opportunities for visualizing subtle prostate tumors, which due to small size, adjacent benign tissue, or a challenging location would otherwise remain undetected by conventional imaging. Achieving high imaging contrast is essential for this purpose and the molecular design of any probe for molecular imaging of prostate cancer should be aimed at obtaining as high tumor-to-organ ratios as possible.OBJECTIVE: This short review summarizes the key imaging modalities currently used in prostate cancer, with a special focus on radionuclide molecular imaging. Emphasis is laid mainly on the issue of radiometals labeling chemistry and its influence on the targeting properties and biodistribution of radiolabeled GRPR antagonists for imaging of disseminated prostate cancer.METHODS: A comprehensive literature search of the PubMed/MEDLINE, and Scopus library databases was conducted to find relevant articles.RESULTS: The combination of radionuclide, chelator and required labeling chemistry was shown to have a significant influence on the stability, binding affinity, and internalization rate, off-target interaction with normal tissues and blood proteins, interaction with enzymes, activity uptake and retention in excretory organs and activity uptake in tumors of radiolabeled bombesin antagonistic analogues.CONCLUSION: Labeling chemistry had a very strong impact on the biodistribution profile of GRPR-targeting peptide based imaging probes and needs to be considered when designing a targeting probe for high contrast molecular imaging. Taking into account the complexity of in vivo interactions, it is not currently possible to accurately predict the optimal labeling approach. Therefore, a detailed characterization and optimization is essential for the rational design of imaging agents.
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| 5. |
- O' Donovan, Daniel H., et al.
(författare)
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The Next Generation of Pattern Recognition Receptor Agonists : Improving Response Rates in Cancer Immunotherapy
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:34, s. 5654-5674
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Tidskriftsartikel (refereegranskat)abstract
- The recent success of checkpoint blocking antibodies has sparked a revolution in cancer immunotherapy. Checkpoint inhibition activates the adaptive immune system leading to durable responses across a range of tumor types, although this response is limited to patient populations with pre-existing tumor infiltrating T cells. Strategies to stimulate the immune system to prime an antitumor response are of intense interest and several groups are now working to develop agents to activate the pattern recognition receptors (PRRs), proteins which detect pathogenic and damage-associated molecules and respond by activating the innate immune response. Although early efforts focused on the Toll-like receptor (TLR) family of membrane-bound PRRs, TLR activation has been associated with both pro- and antitumor effects. Nonetheless, TLR agonists have been deployed as potential anticancer agents in a range of clinical trials. More recently, the cytosolic PRR Stimulator of IFN genes (STING) has attracted attention as another promising target for anticancer drug development, with early clinical data beginning to emerge. Besides STING, several other cytosolic PRR targets have likewise captured the interest of the drug discovery community, including the RIG-I-like receptors (RLRs) and NOD-like receptors (NLRs). In this review, we describe the outlook for activators of PRRs as anticancer therapeutic agents and contrast the earlier generation of TLR agonists with the emerging focus on cytosolic PRR activators, both as single agents and in combination with other cancer immunotherapies.
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| 6. |
- Rolla, Giovanni, et al.
(författare)
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An Emerging Role for Exhaled Nitric Oxide in Guiding Biological Treatment in Severe Asthma
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 27:42, s. 7159-7167
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Forskningsöversikt (refereegranskat)abstract
- Asthma is a heterogeneous disease with regard to the inflammatory pathways activated. In recent years, biologic drugs (monoclonal antibodies) directed towards specific components of type 2 inflammation have been approved for the treatment of severe asthma. Phenotyping of patients with severe asthma and evaluation of biomarkers have been recommended to help identify patients who are candidates for treatment with biologics and to monitor treatment responses.Fractional exhaled Nitric Oxide (FeNO) is a biomarker of type 2 inflammation in asthma, signaling activation of Interleukin (IL)-4/IL-13 pathway. FeNO could be useful to assess treatment response or identify candidates for a specific drug that acts on type 2 inflammation mechanisms linked to Nitric Oxide (NO) production, such as the IL-4/IL-13 pathway or upstream processes.The value of FeNO as a biomarker predictive of responses to the biologics available for treating severe asthma is discussed based on the published studies at the moment of the review.
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| 7. |
- Simeon, Saw, et al.
(författare)
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Characterizing the Relationship Between the Chemical Structures of Drugs and their Activities on Primary Cultures of Pediatric Solid Tumors
- 2021
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers. - 0929-8673 .- 1875-533X. ; 28:38, s. 7830-7839
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Despite continued efforts to develop new treatments, there is an urgent need to discover new drug leads to treat tumors exhibiting primary or secondary resistance to existing drugs. Cell cultures derived from patient-derived orthotopic xenografts are promising pre-clinical models to better predict drug response in cancer recurrence.OBJECTIVE: The aim of the study was to investigate the relationship between the physiochemical properties of drugs and their in vitro potency as well as identifying chemical scaffolds biasedtowards selectivity or promiscuity of such drugs.METHODS: The bioactivities of 158 drugs screened against cell cultures derived from 30 cancer orthotopic patient-derived xenograft (O-PDX) models were considered. Drugs were represented by physicochemical descriptors and chemical structure fingerprints. Supervised learning was employed to model the relationship between features and in vitro potency.RESULTS: Drugs with in vitro potency for alveolar rhabdomyosarcoma and osteosarcoma tend to have a higher number of rings, two carbon-hetero bonds and halogens. Selective and promiscuous scaffolds for these phenotypic targets were identified. Highly-predictive models of in vitro potency were obtained across these 30 targets, which can be applied to unseen molecules via a webserver (https://rnewbie.shinyapps.io/Shobek-master).CONCLUSION: It is possible to identify privileged chemical scaffolds and predict the in vitro potency of unseen molecules across these 30 targets This information and models should be helpful to select which molecules to screen against these primary cultures of pediatric solid tumors.
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| 8. |
- Wen, Kangmei, et al.
(författare)
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Recent Research on Flavonoids and their Biomedical Applications
- 2021
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Ingår i: Current Medicinal Chemistry. - Sharjah : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 28:5, s. 1042-1066
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Forskningsöversikt (refereegranskat)abstract
- Flavonoids, commonly found in various plants, are a class of polyphenolic compounds having a basic structural unit of 2-phenylchromone. Flavonoid compounds have attracted much attention due to their wide biological applications. In order to facilitate further research on the biomedical application of flavonoids, we surveyed the literature published on the use of flavonoids in medicine during the past decade, documented the commonly found structures in natural flavonoids, and summarized their pharmacological activities as well as associated mechanisms of action against a variety of health disorders including chronic inflammation, cancer, cardiovascular complications and hypoglycemia. In this mini-review, we provide suggestions for further research on the biomedical applications of flavonoids. © Bentham Science Publishers
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| 9. |
- Zhang, Zhenzhan, et al.
(författare)
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Drug Repurposing in Oncology : Current Evidence and Future Direction
- 2020
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673. ; 28:11, s. 2175-2194
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Drug repurposing, the application of known drugs and compounds with a non-oncology primary purpose, might be an attractive strategy to offer more effective treatment options to patients with cancer at a low cost and reduced time.METHODS: This review described a total of 10 kinds of non-oncological drugs from more than 100 mechanical studies as well as evidence from population-based studies. The future direction of repurposed drug screening was discussed by using patient-derived tumor organoids.RESULTS: Many old drugs showed previously unknown effects or off-target effects and can be intelligently applied for cancer chemoprevention and therapy. The identification of repurposed drugs needs to combine evidence from mechanical studies and population-based studies. Due to the heterogeneity of cancer, patient-derived tumor organoids can be used to screen the non-oncological drugs in vitro.CONCLUSION: These identified old drugs could be repurposed in oncology and might be added as adjuvants and finally benefit patients with cancers.
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