Synthesis, biological activity and molecular modeling studies of novel COX-1 inhibitors.

Article Details

Citation

Martic M, Tatic I, Markovic S, Kujundzic N, Kostrun S

Synthesis, biological activity and molecular modeling studies of novel COX-1 inhibitors.

Eur J Med Chem. 2004 Feb;39(2):141-51.

PubMed ID
14987823 [ View in PubMed
]
Abstract

Synthesis of new potential COX-1 and/or COX-2 inhibitors, derivatives of 1,1-di-(3-carboxyphenyl)ethane, their biological activity, docking results on COX-1 enzyme and absorption, distribution, metabolism, excretion (ADME) properties are presented. In addition to known interactions between ketoprofen and ibuprofen, leading NSAID agents and COX-1 active site, the possibility of formation of additional interactions is explored. Interactions with Ala527, and with one of the water molecules situated within the active site are identified. Molecular mechanics and DFT calculations for studied compounds have revealed free rotation around two central bonds (C1-C3' and C1-C3"), making them flexible, thus easier to enter and adjust to the active site. Further modifications of core structure have been undertaken to optimize biological activity and ADME properties. As a result, two of the compounds are indicated as novel COX-1 inhibitors.

DrugBank Data that Cites this Article

Drug Targets
DrugTargetKindOrganismPharmacological ActionActions
IbuprofenProstaglandin G/H synthase 1ProteinHumans
Yes
Inhibitor
Details
KetoprofenProstaglandin G/H synthase 1ProteinHumans
Unknown
Inhibitor
Details
Tiaprofenic acidProstaglandin G/H synthase 1ProteinHumans
Yes
Inhibitor
Details