Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives

Srivastava, Pavan; Vyas, Vivek K.; Variya, Bhavesh C.; Patel, Palak; Qureshi, Gulamnizami; Ghate, Manjunath

doi:10.1016/j.bioorg.2016.06.004

Cited by 81 publications

(45 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In 2016, Srivastava and colleagues evaluated the anti-inflammatory and analgesic effect of a series of synthesized 7-substituted coumarins and, consequently, the most active compounds were assessed in vitro for 5-LOX inhibition [146]. Compounds 101 and 102 ( Figure 35) resulted the most promising derivatives, also in the ulcerogenic risk evaluation when compared to acetylsalicylic acid.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

Annunziata

Pinna

Dallavalle

et al. 2020

IJMS

283

156

View full text Add to dashboard Cite

Privileged structures have been widely used as an effective template for the research and discovery of high value chemicals. Coumarin is a simple scaffold widespread in Nature and it can be found in a considerable number of plants as well as in some fungi and bacteria. In the last years, these natural compounds have been gaining an increasing attention from the scientific community for their wide range of biological activities, mainly due to their ability to interact with diverse enzymes and receptors in living organisms. In addition, coumarin nucleus has proved to be easily synthetized and decorated, giving the possibility of designing new coumarin-based compounds and investigating their potential in the treatment of various diseases. The versatility of coumarin scaffold finds applications not only in medicinal chemistry but also in the agrochemical field as well as in the cosmetic and fragrances industry. This review is intended to be a critical overview on coumarins, comprehensive of natural sources, metabolites, biological evaluations and synthetic approaches.

show abstract

Section: Anti-inflammatory Activitymentioning

confidence: 99%

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

Annunziata

Pinna

Dallavalle

et al. 2020

IJMS

283

156

View full text Add to dashboard Cite

show abstract

“…In 2016, compounds 12a and 12b, types of 7-subsituted coumarin derivatives, were identified by Ghate et al Their IC 50 values against LOX were 2.8 and 2.1 μM, respectively. 45 The mechanism of 12b against LOX could be either non-competitive inhibition or both noncompetitive and competitive inhibition. Their structural difference was that 12a has a chlorine atom at the C6-position of benzothiazole while 12b has a methoxy group.…”

Section: Inhibitors Obtained By the Modification Of Previously Known mentioning

confidence: 99%

Recent development of lipoxygenase inhibitors as anti-inflammatory agents

2018

Med. Chem. Commun.

View full text Add to dashboard Cite

Inflammation is favorable in most cases, because it is a kind of body defensive response to external stimuli; sometimes, inflammation is also harmful, such as attacks on the body's own tissues. It could be that inflammation is a unified process of injury and resistance to injury. Inflammation brings extreme pain to patients, showing symptoms of rubor, swelling, fever, pain and dysfunction. As the specific mechanism is not clear yet, the current anti-inflammatory agents are given priority for relieving suffering of patients. Thus it is emergent to find new anti-inflammatory agents with rapid effect. Lipoxygenase (LOX) is a kind of rate-limiting enzyme in the process of arachidonic acid metabolism into leukotriene (LT) which mediates the occurrence of inflammation. The inhibition of LOX can reduce LT, thereby producing an anti-inflammatory effect. In this review, the LOX inhibitors reported in recent years are summarized, and, in particular, their activities, structure-activity relationships and molecular docking studies are emphasized, which will provide new ideas to design novel LOX inhibitors.

show abstract

“…Most of the LOX inhibitors are antioxidants or free radical scavengers since lipoxygenation occurs via a carbon-centered radical. Coumarin derivatives have demonstrated effective lipoxygenase (LOX) inhibition activity [ 25 , 26 ]. An unsubstituted phenyl ring and compounds with a 2-Me group on the phenyl ring and higher lipophilicity values showed good anti-inflammatory activity [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study

et al. 2020

View full text Add to dashboard Cite

Lipoxygenases (LOXs) are a family of enzymes found in plants, mammals, and microorganisms. In animals and plants, the enzyme has the capability for the peroxidation of unsaturated fatty acids. Although LOXs participate in the plant defense system, the enzyme’s metabolites can have numerous negative effects on human health. Therefore, many types of research are searching for compounds that can inhibit LOXs. The best quantitative structure–activity relationship (QSAR) model was obtained using a Genetic Algorithm (GA). Molecular docking was performed with iGEMDOCK. The inhibition of lipoxygenase was in the range of 7.1 to 96.6%, and the inhibition of lipid peroxidation was 7.0–91.0%. Among the synthesized compounds, the strongest inhibitor of soybean LOX-3 (96.6%) was found to be 3-benzoyl-7-(benzyloxy)-2H-chromen-2-one. A lipid peroxidation inhibition of 91.0% was achieved with ethyl 7-methoxy-2-oxo-2H-chromene-3-carboxylate. The docking scores for the soybean LOX-3 and human 5-LOX also indicated that this compound has the best affinity for these LOX enzymes. The best multiple linear QSAR model contains the atom-centered fragment descriptors C-06, RDF035p, and HATS8p. QSAR and molecular docking studies elucidated the structural features important for the enhanced inhibitory activity of the most active compounds, such as the presence of the benzoyl ring at the 3-position of coumarin’s core. Compounds with benzoyl substituents are promising candidates as potent lipoxygenase inhibitors.

show abstract

Synthesis, anti-inflammatory, analgesic, 5-lipoxygenase (5-LOX) inhibition activities, and molecular docking study of 7-substituted coumarin derivatives

Cited by 81 publications

References 22 publications

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

An Overview of Coumarin as a Versatile and Readily Accessible Scaffold with Broad-Ranging Biological Activities

Recent development of lipoxygenase inhibitors as anti-inflammatory agents

Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study

Contact Info

Product

Resources

About