scholarly journals Molecular modeling and structural analysis of some tetrahydroindazole and cyclopentanepyrazole derivatives as COX-2 Inhibitors

2021 ◽  
pp. 103540
Author(s):  
Efraín Polo-Cuadrado ◽  
Karen Acosta-Quiroga ◽  
Cristian Rojas-Peña ◽  
Yeray A. Rodriguez-Nuñez ◽  
Yorley Duarte ◽  
...  
Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3550
Author(s):  
Katharigatta N. Venugopala ◽  
Sandeep Chandrashekharappa ◽  
Christophe Tratrat ◽  
Pran Kishore Deb ◽  
Rahul D. Nagdeve ◽  
...  

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (5a–e) were carried out and evaluated for COX-2 enzyme inhibition. All the compounds showed activity in micromolar ranges, and the compound diethyl 3-(4-cyanobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5a) emerged as a promising COX-2 inhibitor with an IC50 of 5.84 µM, as compared to indomethacin (IC50 = 6.84 µM). The molecular modeling study of indolizines indicated that hydrophobic interactions were the major contribution to COX-2 inhibition. The title compound diethyl 3-(4-bromobenzoyl)-7-methoxyindolizine-1,2-dicarboxylate (5c) was subjected for single-crystal X-ray studies, Hirshfeld surface analysis, and energy framework calculations. The X-ray diffraction analysis showed that the molecule (5c) crystallizes in the monoclinic crystal system with space group P 21/n with a = 12.0497(6)Å, b = 17.8324(10)Å, c = 19.6052(11)Å, α = 90.000°, β = 100.372(1)°, γ = 90.000°, and V = 4143.8(4)Å3. In addition, with the help of Crystal Explorer software program using the B3LYP/6-31G(d, p) basis set, the theoretical calculation of the interaction and graphical representation of energy value was measured in the form of the energy framework in terms of coulombic, dispersion, and total energy.


2019 ◽  
Vol 4 (37) ◽  
pp. 11081-11092
Author(s):  
Satyanarayana Yatam ◽  
Surender Singh Jadav ◽  
Krishna Prasadh Gundla ◽  
Kalyani Paidikondala ◽  
Ashok Reddy Ankireddy ◽  
...  

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 661 ◽  
Author(s):  
Venugopala ◽  
Al-Attraqchi ◽  
Tratrat ◽  
Nayak ◽  
Morsy ◽  
...  

The cyclooxygenase-2 (COX-2) enzyme is considered to be an important target for developing novel anti-inflammatory agents. Selective COX-2 inhibitors offer the advantage of lower adverse effects that are commonly associated with non-selective COX inhibitors. In this work, a novel series of methyl 3-(substituted benzoyl)-7-substituted-2-phenylindolizine-1-carboxylates was synthesized and evaluated for COX-2 inhibitory activity. Compound 4e was identified as the most active compound of the series with an IC50 of 6.71 M, which is comparable to the IC50 of indomethacin, a marketed non-steroidal anti-inflammatory drug (NSAID). Molecular modeling and crystallographic studies were conducted to further characterize the compounds and gain better understanding of the binding interactions between the compounds and the residues at the active site of the COX-2 enzyme. The pharmacokinetic properties and potential toxic effects were predicted for all the synthesized compounds, which indicated good drug-like properties. Thus, these synthesized compounds can be considered as potential lead compounds for developing effective anti-inflammatory therapeutic agents.


2015 ◽  
Vol 25 (9) ◽  
pp. 1947-1951 ◽  
Author(s):  
Zhong Chen ◽  
Zhong-Chang Wang ◽  
Xiao-Qiang Yan ◽  
Peng-Fei Wang ◽  
Xiao-Yuan Lu ◽  
...  

2015 ◽  
Vol 348 (12) ◽  
pp. 875-888 ◽  
Author(s):  
Dina H. Dawood ◽  
Rasha Z. Batran ◽  
Thoraya A. Farghaly ◽  
Mohammed A. Khedr ◽  
Mohamed M. Abdulla

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