Cyclic enaminone as new chemotype for selective cyclooxygenase-2 inhibitory, anti-inflammatory, and analgesic activities

Kumar, Raj; Saha, N. N.; Purohit, Priyank; Garg, Sanjeev; Seth, Kapileswar; Meena, Vachan Singh; Dubey, Sachin; Dave, Khyati; Goyal, Rohit; Sharma, Shyam Sundar; Banerjee, Uttam Chand; Chakraborti, Asit K.

doi:10.1016/j.ejmech.2019.111601

Cited by 27 publications

(10 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results demonstrated that three compounds ( 105a , 105b , and 105c ( Figure 19 )) predominantly inhibited COX-2, with SIs of 74.09, 108.68, and 19.45, respectively. The anti-inflammatory potency of compound 105a was comparable to that of celecoxib at a dose of 12.5 mg/kg, and compounds 105b and 105c were more/equally effective compared to celecoxib at 12.5 and 25 mg/kg doses 120 .…”

Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 87%

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Bian

Wu³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

Inflammation and disease are closely related. Inflammation can induce various diseases, and diseases can promote inflammatory response, and two possibly induces each other in a bidirectional loop. Inflammation is usually treated using synthetic anti-inflammatory drugs which are associated with several adverse effects hence are not safe for long-term use. Therefore, there is need for anti-inflammatory drugs which are not only effective but also safe. Several researchers have devoted to the research and development of effective anti-inflammatory drugs with little or no side effects. In this review, we studied some small molecules with reported anti-inflammatory activities and hence potential sources of anti-inflammatory agents. The information was retrieved from relevant studies published between January 2019 and May, 2021 for review. This review study was aimed to provide relevant information towards the design and development of effective and safe anti-inflammation agents.

show abstract

Section: Recent Development In Anti-inflammatory Agentsmentioning

confidence: 87%

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Bian

Wu³

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…That is what made them very useful as intermediates in the synthesis of acyclic, cyclic, and heterocyclic systems [2][3][4][5][6]. Besides their use as precursors, β-enaminone-containing molecules have also been employed for medical purposes and remained very useful, showing several activities such as antibacterial [7], antitubercular [8], anti-inflammatory [9], anticonvulsant [10], antitumoral [11], antinociceptive [12], and antidepressant activities [13]. More recently, they have been identified as non-classical inhibitors of carbonic anhydrase [14] (Fig.…”

Section: Introductionmentioning

confidence: 99%

New efficient synthesis, spectroscopic characterization, and X-ray analysis of novel β-enaminocarboxamide derivatives

et al. 2023

View full text Add to dashboard Cite

A new series of β-enaminocarboxamide was synthesized via the addition of chlorosulfonyl isocyanate to β-enaminones. The prepared intermediates were converted to corresponding β-enaminocarboxamides by removal of the chlorosulfonyl group using methanol. The resulting compounds were obtained in excellent yields in the range of (80-92%) and were characterized by 1 H, 13 C, HMBC, HSQC NMR spectroscopy, and IR spectroscopy as well as elemental analysis. 1 H-NMR spectrum showed a non-equivalence of the primary amide protons which was due to H-bonding. β-enaminocarboxamide 5h was obtained as a crystal and was subjected to X-ray analysis. Results showed that 5h crystallizes in the monoclinic crystal system with C2/c space group and the ORTEP confirmed the presence of intramolecular H-bonds.

show abstract

“…Inflammation has been treated for decades with a variety of COX inhibitors, namely, a cetylsalicylic acid and indomethacin. However, some side effects, including as bronchospasm, angioedema and renal dysfunction, as well as bone marrow depression, headache and vertigo, have been reported during their use [ 8 , 9 ]. As a result, finding novel and innovative COX-2 inhibitors with enhanced potency and selectivity is a source of growing worry for the medical community.…”

Section: Introductionmentioning

confidence: 99%

Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-inflammatory agent against COX-2

Jack

Asaruddin

Bhawani

2022

Chem. Biol. Technol. Agric.

View full text Add to dashboard Cite

Background Virgin coconut oil is mostly made up of saturated fatty acids in which approximately 72% are medium chain triglycerides. Medium chain triglycerides can be digested into medium chain fatty acids and medium chain monoglycerides which are bioactive components. Therefore, it is very important to study the in-silico ability of some Virgin coconut oil derivatives, namely, medium chain fatty acids and medium chain monoglycerides to inhibit Cyclooxygenase 2 (COX-2) protein for prevention of excessive inflammatory response. Results Pharmacophore study displayed monolaurin with two hydrogen bond donor, three hydrogen bond acceptor and five hydrophobic interactions, while lauric acid presented two hydrogen bond acceptor, five hydrophobic interactions and a negative ion interaction. Molecular docking underlined the ability of monolaurin in the inhibition of COX-2 protein which causes inflammatory action with a decent result of energy binding affinity of − 7.58 kcal/mol and 15 interactions out of which 3 are strong hydrogen bond with TYR385 (3.00 Å), PHE529 (2.77 Å), and GLY533 (3.10 Å) residues of the protein. Monolaurin was employed as hydrogen bond acceptor to the side of residue TYR385 of COX-2 protein with an occupancy of 67.03% and was observed to be long-living during the entire 1000 frames of the molecular dynamic simulation. The analysis of RMSD score of the Monolaurin–COX-2 complex backbone was calculated to be low (1.137 $$\pm$$ ± 0.153 Å) and was in a stable range of 0.480 to 1.520 Å. Redocking of this complex still maintained a strong hydrogen bond (2.87 Å) with the main residue TYR385. AMDET results where promising for medium chain fatty acids and medium chain monoglycerides with good physicochemical drug scores. Conclusions This can be concluded from the results obtained that the monolaurin has strong interactions with COX-2 protein to disrupt its function due to significant hydrogen bonds and hydrophobic interactions with amino acid residues present in the target protein’s active site. These results displayed a very significant anti-inflammatory potential of monolaurin and a new promising drug candidates as anti-inflammatory agent. Graphical Abstract

show abstract

Cyclic enaminone as new chemotype for selective cyclooxygenase-2 inhibitory, anti-inflammatory, and analgesic activities

Cited by 27 publications

References 65 publications

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

Small molecule compounds with good anti-inflammatory activity reported in the literature from 01/2009 to 05/2021: a review

New efficient synthesis, spectroscopic characterization, and X-ray analysis of novel β-enaminocarboxamide derivatives

Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-inflammatory agent against COX-2

Contact Info

Product

Resources

About