Therapeutic Antibody‐Based Drugs in the Treatment of Human Inflammatory Disorders

: Cancer and inflammatory disorders are two important public health issues worldwide with significant socio.economic impacts. Despite several efforts, the current therapeutic platforms are associated with severe limitations. Therefore, developing new therapeutic strategies for the treatment of these diseases is a top priority. Besides current therapies, the utilization of natural compounds has emerged as a new horizon for the treatment of cancer and inflammatory disorders as well. Such natural compounds could be used either alone or in combination with the standard cancer therapeutic modalities such as chemotherapy, radiotherapy, and immunotherapy. Resveratrol is a polyphenolic compound that is found in grapes as well as other foods. It has been found that this medicinal agent displays a wide pharmacological spectrum, including anti-cancer, anti-inflammatory, anti-microbial, and antioxidant activities. Recently, clinical and pre-clinical studies have highlighted the anti-cancer and anti-inflammatory effects of resveratrol. Increasing evidence revealed that resveratrol exerts its therapeutic effects by targeting various cellular and molecular mechanisms. Among cellular and molecular targets that are modulated by resveratrol, microRNAs (miRNAs) have appeared as key targets. MiRNAs are short non-coding RNAs that act as epigenetic regulators. These molecules are involved in many processes that are involved in the initiation and progression of cancer and inflammatory disorders. Herein, we summarized various miRNAs that are directly/indirectly influenced by resveratrol in cancer and inflammatory disorders.

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Herbal Products for Common Auto-Inflammatory Disorders - Novel Approaches

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207321666180213093449 ◽

2018 ◽

Vol 21 (3) ◽

pp. 161-174 ◽

Cited By ~ 7

Author(s):

Shanoo Suroowan ◽

Fawzi Mahomoodally

Keyword(s):

Adverse Effects ◽

Chronic Conditions ◽

Herbal Medicines ◽

Review Article ◽

Herbal Products ◽

Inflammatory Disorders ◽

Treatment Regimens ◽

Synthetic Agents ◽

Unique Approach ◽

Novel Approaches

Background: Common auto-inflammatory disorders (CAIDs) constitute a wide array of ailments ranging from acute allergies to chronic conditions. Globally, CAIDs remain one of the leading causes of disability and morbidity. Despite playing a leading therapeutic role, the vast profusion of anti-inflammatory synthetic agents have not been able to fully resolve a panoply of CAIDs. Additionally, contemporary synthetic therapy approaches remain bounded by a wide array of limitations essentially being adverse effects and unaffordable costs. In this advent, the use of herbal products provides an interesting avenue to explore in view of developing such treatment regimens. Objective: This review article endeavors to highlight potential herbal products and isolated phytochemicals which can be of benefit in the prophylaxis, management, and treatment alongside avoiding the relapse of CAIDs. Conclusion: This review article has highlighted that herbals, herbal products, and isolated metabolites hold a huge potential in the prophylaxis, management, and treatment of CAIDs. Herbals can act on various targets involved in the pathogenesis of inflammatory disorders. In addition, novel approaches for the management of CAIDs are numerous. Indeed, nanoparticles loaded with phytochemicals have been developed to specifically target the colon for IBD treatment. In silico approaches using herbals also offer unlimited avenues to decipher new pharmacophores. Investigating the potential of polyherbal formulations is another unique approach which can be investigated. Given the inefficacy of conventional medicines, the concomitant use of conventional and herbal medicines can also be explored.

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Inhibitors of Nitrogen Oxide Species Production in Animal Models of Inflammation and Future Directions for Therapy in Inflammatory Disorders

Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents ◽

10.2174/1568014043355339 ◽

2004 ◽

Vol 3 (3) ◽

pp. 239-259 ◽

Cited By ~ 3

Author(s):

Francois Feihl ◽

Mauro Oddo ◽

Bernard Waeber ◽

Lucas Liaudet

Keyword(s):

Animal Models ◽

Nitrogen Oxide ◽

Future Directions ◽

Inflammatory Disorders ◽

Species Production

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Cytokine Gene Polymorphisms in Cancer and Inflammatory Disorders

Current Immunology Reviews ◽

10.2174/1573395514666180724121419 ◽

2018 ◽

Vol 14 (2) ◽

pp. 81-93

Author(s):

Hanim Kamis Norhalifah ◽

Nor Fazila Che Mat ◽

Hisham Atan Edinur

Keyword(s):

Gene Polymorphisms ◽

Cytokine Gene ◽

Inflammatory Disorders ◽

Cytokine Gene Polymorphisms

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ROS Inhibitory Activity and Cytotoxicity Evaluation of Benzoyl, Acetyl, Alkyl Ester, and Sulfonate Ester Substituted Coumarin Derivatives

Medicinal Chemistry ◽

10.2174/1573406415666190826153001 ◽

2020 ◽

Vol 16 (8) ◽

pp. 1099-1111

Author(s):

Uzma Salar ◽

Khalid M. Khan ◽

Almas Jabeen ◽

Aisha Faheem ◽

Farwa Naqvi ◽

...

Keyword(s):

Inhibitory Activity ◽

Antiinflammatory Drug ◽

Vital Role ◽

Alkyl Ester ◽

Flufenamic Acid ◽

Coumarin Derivatives ◽

Inflammatory Disorders ◽

Enhanced Chemiluminescence ◽

Anti Inflammatory ◽

Sulfonate Ester

Background: A number of non-steroidal anti-inflammatory drugs (NSAIDs) including aspirin, indomethacin, ibuprofen, flufenamic acid, and phenylbutazone are being clinically used to treat inflammatory disorders. These NSAIDs are associated with serious side effects such as gastric ulceration, nephrotoxicity, and bleeding. Therefore, the identification of potent and safe therapy for inflammatory disorders is still of great interest to the medicinal chemist. Methods: A series of varyingly substituted benzoyl, acetyl, alkyl ester, and sulfonate ester substituted coumarins 1-64 were screened for the inhibition of ROS, generated from zymosan activated whole blood phagocytes, using luminol-enhanced chemiluminescence technique. Results: Among all tested compounds, 8 (IC50 = 65.0 ± 3.1 μM), 24 (IC50 = 41.8 ± 1.5 μM), 26 (IC50 = 10.6 ± 2.8 μM), 28 (IC50 = 20.9 ± 1.5 μM), and 41 (IC50 = 4.6 ± 0.3 μM) showed good anti- inflammatory potential as compared to standard antiinflammatory drug ibuprofen (IC50 = 54.3 ± 1.9 μM). Specifically, compounds 24, 26, 28, and 41 showed superior activity than standard antiinflammatory drug. Furthermore, compounds 12 (IC50 = 219.0 ± 1.4 μM), 14 (IC50 = 216.5 ± 6.2 μM), 16 (IC50 = 187.4 ± 2.2 μM), and 20 (IC50 = 196.2 ± 2.0 μM) showed moderate ROS inhibitory activity. Limited SAR study revealed that the hydroxy-substituted compound showed better ROS inhibition potential in case of 3-benzoyl and 3-ethylester coumarin derivatives. Whereas, chloro substitution was found to be important in case of 3-acetyl coumarin derivatives. Similarly, in case of sulfonate ester, chloro, and nitro groups especially at positions -4 and -3 of ring “R” played vital role in ROS inhibition. Furthermore, cytotoxicity of all active compounds was also checked on NIH-3T3 cell line. Compounds 12, 14, and 20 were found to be non-cytotoxic. Whereas, 8, 16, 24, 26, 28, and 41 were found to be very weak cytotoxic as compared to standard cycloheximide (IC50 = 0.13 ± 0.02 μM). Conclusion: Identified ROS inhibitors offer the possibility of additional modifications that could give rise to lead structures for further research in order to obtain more potent, and safer antiinflammatory agent.

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