Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX

Bhuktar, Harshavardhan; Shukla, Sharda; Kakularam, Kumar Reddy; Battu, Srikanth; Srikanth, Manupati; Srivastava, Susmita; Medishetti, Raghavender; Ram, P. C.; Jagadish, P C; Rasool, Mahaboobkhan; Chakraborty, Sandipan; Khan, Nooruddin; Reddanna, Pallu; Oruganti, Srinivas; Pal, Manojit

doi:10.1016/j.bioorg.2023.106606

Cited by 4 publications

(3 citation statements)

References 67 publications

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“…Crystal data for polyasper B ( 2 ). C 42 H 50 O 7 , M r = 666.82, a = 24.96200(10) Å, b = 10.874 Å, c = 27.95240(10) Å, α = 90°, β = 115.1500(10)°, γ = 90°, V = 6868.02(6) Å 3 , T = 293(2) K, space group C 2, Z = 8, μ (Cu Kα) = 0.692 mm –1 , 94425 reflections measured, 13735 independent reflections ( R int = 0.0318). The final R 1 values were 0.0297 ( I > 2 σ ( I )).…”

Section: Methodsmentioning

confidence: 99%

“…Psoriasis is an autoimmune chronic systemic disease and is considered to be the most common immune‐mediated disease significantly affecting the quality of life of nearly 3% of the general population worldwide which brings substantial burdens to individuals and society. [ 1‐5 ] Although the detailed pathogenesis of psoriasis is still unclear, it is generally accepted that the pathogenesis of psoriasis is stimulated by keratinocyte hyperproliferation and excessive inflammatory response. [ 6‐10 ] Previous studies have shown that multiple cytokines, such as interleukin (IL)‐17 and tumor necrosis factor‐alpha (TNF‐ α ) are involved in the pathogenesis of psoriasis vulgaris.…”

Section: Background and Originality Contentmentioning

confidence: 99%

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Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Hu,

Li,

Shi

et al. 2023

Chin. J. Chem.

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Comprehensive SummaryPsoriasis is a chronic immune‐mediated inflammatory skin disease and the TNF‐α is an important therapeutic target of this disease. In our continuous study of bioactive natural products from fungi, the first ergosterol‐polyether adducts, polyaspers A (1) and B (2), along with two known ergosterols, (3β,5α,6α,22E)‐5,6‐epoxy‐3‐hydroxyergosta‐8,22‐dien‐7‐one (3) and calvasterol B (4), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and single‐crystal X‐ray diffraction tests. Polyaspers A and B possessing an unequalled 6/6/6/5/5/6/6/6/6 nonacyclic system, and their biosynthetic pathways were proposed to include intermolecular cyclization and Diels‐Alder reactions. Activity screen of these isolates showed that 1—3 could improve the cell viability in an actinomycin D/TNF‐α induced L929 cells death model, with the EC50 values of 49.85, 46.75 and 4.99 μmol/L, respectively, and the activity of 3 was even comparable with that of the positive control SPD304. Further bioactive investigations discovered 3 could suppress the inflammatory response simulated with TNF‐α in HaCaT cells. In an imiquimod‐induced psoriasis murine model, 3 significantly restrained the development of psoriasis symptoms and reduced the expression of IL‐17 and IL‐23, presenting an anti‐psoriatic effect. As such, those ergosterol derivatives, might serve as lead compounds for the development of novel TNF‐α inhibitory agents in the clinical treatment of psoriasis.

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Section: Methodsmentioning

confidence: 99%

Section: Background and Originality Contentmentioning

confidence: 99%

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Hu,

Li,

Shi

et al. 2023

Chin. J. Chem.

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“…These proteins have garnered significant attention in medical research and therapeutic development due to their potential to address a broad spectrum of inflammatory conditions, including autoimmune diseases, chronic inflammation, and inflammatory responses linked to infections or tissue damage. The major psoriasis inflammatory markers includes IL-23 [4], IL-17 [5], IL-6 [6], TNF-α [4], NLRP-3 [7], and 12R Lipoxygenase [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders

Swain,

Maddi

2024

JDDMC

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Psoriasis is an inflammatory skin disease in which the immune system's T cells are activated and trigger inflammation within the skin. Inflammatory markers, such as IL-23, IL-17, IL-6, TNF-α, NLRP-3, and 12R Lipoxygenase (12 R-Lox), play a crucial role in the inflammatory pathway. Anti-inflammatory drugs are used to modulate the immune response and reduce excessive inflammation that contributes to disease progression. However, many existing anti-inflammatory drugs often target a single marker, potentially limiting their effectiveness and leading to side effects. Emerging research has highlighted the potential of various phytochemicals to modulate inflammatory processes and contribute to improved health outcomes. This study aimed to explore the potential of phytochemicals as alternative therapeutic agents targeting multiple psoriasis inflammatory biomarkers. In silico molecular docking was conducted on various phytochemicals, including curcumin, mangiferin, reservatrol, silybin, quercertin, piperine, and naringin against different inflammatory biomarkers: IL-6, IL-17, IL-23, TNF-α, NLRP-3 and 12R-Lox. The results illustrated that among the phytochemicals, silybin exhibited the highest docking score and inhibiting effects on all the inflammatory biomarkers. Curcumin, mangiferin, silybin and piperine demonstrated binding with multiple inflammatory biomarkers. Additionally, 12R-Lox displayed the highest binding affinity with all the phytochemicals. The inhibition and binding effects of the remaining phytochemicals under evaluation were moderate. The combination of these phytochemicals can be used for the preparation of medications targeting psoriasis.

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Bioisosteric heterocyclic analogues of natural bioactive flavonoids by scaffold-hopping approaches: State-of-the-art and perspectives in medicinal chemistry

La Monica,

Bono,

Alamia

et al. 2024

Bioorganic & Medicinal Chemistry

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Design, synthesis and evaluation of 2-aryl quinoline derivatives against 12R-lipoxygenase (12R-LOX): Discovery of first inhibitor of 12R-LOX

Cited by 4 publications

References 67 publications

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Polyaspers A and B, the First Ergosterol‐Polyether Adducts with Unprecedented 6/6/6/5/5/6/6/6/6 Nonacyclic Architecture from Aspergillus sp. TJ507

Molecular Interaction Analysis of Phytochemicals as the Prospective Potential Multi-Target Inhibitors Related to Psoriasis and Other Autoimmune Disorders

Bioisosteric heterocyclic analogues of natural bioactive flavonoids by scaffold-hopping approaches: State-of-the-art and perspectives in medicinal chemistry

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