Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids
2011
Autori
Savić, JelenaDilber, Sanda
Marković, Bojan
Milenković, Marina
Vladimirov, Sote
Juranić, Ivan O.
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect a-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 mu mol/kg and 15 mu mol/kg, while the result for ibuprofen is 51.7 mu mol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. T...he results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenylpropanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.
Ključne reči:
beta-hydroxy-beta-arylpropanoic acids / Reformatsky reaction / anti-inflammatory activity / molecular docking simulations / COX-2 selective inhibitorIzvor:
Molecules, 2011, 16, 8, 6645-6655Izdavač:
- MDPI, Basel
Finansiranje / projekti:
DOI: 10.3390/molecules16086645
ISSN: 1420-3049
PubMed: 25134768
WoS: 000294249100036
Scopus: 2-s2.0-80052214202
Institucija/grupa
PharmacyTY - JOUR AU - Savić, Jelena AU - Dilber, Sanda AU - Marković, Bojan AU - Milenković, Marina AU - Vladimirov, Sote AU - Juranić, Ivan O. PY - 2011 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1483 AB - Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect a-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 mu mol/kg and 15 mu mol/kg, while the result for ibuprofen is 51.7 mu mol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenylpropanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions. PB - MDPI, Basel T2 - Molecules T1 - Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids VL - 16 IS - 8 SP - 6645 EP - 6655 DO - 10.3390/molecules16086645 ER -
@article{ author = "Savić, Jelena and Dilber, Sanda and Marković, Bojan and Milenković, Marina and Vladimirov, Sote and Juranić, Ivan O.", year = "2011", abstract = "Six beta-hydroxy-beta-aryl propanoic acids were synthesised using a modification of Reformatsky reaction which has already been reported. These acids belong to the aryl propanoic acid class of compounds, structurally similar to the NSAIDs, such as ibuprofen, and an anti-inflammatory activity is thus expected. The aim of this work was to determine anti-inflammatory activity, examine gastric tolerability, and to carry out molecular docking experiments to identify potential COX-2 inhibitors among the beta-hydroxy-beta-aryl propanoic acids, and to elucidate the effect a-methyl substitution on the anti-inflammatory activity. Anti-inflammatory activity and gastric tolerability were determined on rats using carragenan induced paw oedema method, and docking studies were carried out using Autodock v4.0.1. The range of ED(50) values is between 127 mu mol/kg and 15 mu mol/kg, while the result for ibuprofen is 51.7 mu mol/kg. Only slight hyperaemia or few petechiae were spotted on rat's stomach. The results indicate that all compounds possess significant anti-inflammatory activity after oral administration, and that 2-methyl-3-hydroxy-3,3-diphenylpropanoic acid has greatest activity, surpassing that of ibuprofen, a standard NSAID. Another compound, 3-hydroxy-3,3-diphenylpropanoic acid, shows activity matching that of ibuprofen, and is non-chiral and is proven to be non-toxic. The most of investigated compounds have interactions with P3 anchor site like COX-2 selective inhibitors. No tested substances or ibuprofen produced any significant gastric lesions.", publisher = "MDPI, Basel", journal = "Molecules", title = "Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids", volume = "16", number = "8", pages = "6645-6655", doi = "10.3390/molecules16086645" }
Savić, J., Dilber, S., Marković, B., Milenković, M., Vladimirov, S.,& Juranić, I. O.. (2011). Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids. in Molecules MDPI, Basel., 16(8), 6645-6655. https://doi.org/10.3390/molecules16086645
Savić J, Dilber S, Marković B, Milenković M, Vladimirov S, Juranić IO. Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids. in Molecules. 2011;16(8):6645-6655. doi:10.3390/molecules16086645 .
Savić, Jelena, Dilber, Sanda, Marković, Bojan, Milenković, Marina, Vladimirov, Sote, Juranić, Ivan O., "Docking Studies and alpha-Substitution Effects on the Anti-Inflammatory Activity of beta-Hydroxy-beta-arylpropanoic Acids" in Molecules, 16, no. 8 (2011):6645-6655, https://doi.org/10.3390/molecules16086645 . .