АФС

Substance identification

API (APHS) is an O-acetyl-S-alkyl thioester of 2-thiophenol, an acetylating inhibitor of cyclooxygenase-2. English name APHS, CAS 209125-28-0, chemical formula C15H20O2S. Classification section - amides.

Synonyms

• 2-(2-Heptynylthio)-phenol acetate
• o-(Acetophenyl)hept-2-inyl sulfide
• o-(Acetoxyphenyl)hept-2-ynyl sulfide

Physico-chemical characteristics

• Molecular Weight: 264.38
• Exact weight: 262.103
• DSSTox ID: DTXSID40175069
• PSA characteristic: 51.6
• XLogP3: 4.3

Mechanism of action

APS is a selective inhibitor of cyclooxygenase-2 (COX-2), irreversibly modifying the enzyme by acetylation of the Ser530 serine residue. The compound inhibits both COX-1 and COX-2, with IC50 values ​​of 17 μM and 0.8 μM, respectively, for the human recombinant isoforms, making it approximately 60 times more reactive and 100 times more selective for COX-2 compared to acetylsalicylic acid (aspirin). The ability of APS to block HIV-1 replication, presumably through interaction with the process of reverse transcription of the virus, has been described separately.

Chemical features

The acetoxy group on the phenolic ring acts as a transferable acetyl label: in the active site of the enzyme, it is transferred to the hydroxyl group of serine Ser530, ​​irreversibly blocking the catalytic activity of cyclooxygenase, while the released thiophenol fragment with a heptynyl substituent determines the orientation of the molecule in the hydrophobic channel of the active center. This mechanism of acetylation transfer is structurally related to the effect of aspirin on COX-1, but due to the bulky alkynyl substituent, APS selectively interacts with the more spacious active site of COX-2. The moderate lipophilicity of the compound (XLogP3 4.3) with a relatively small polar surface area (PSA 51.6) facilitates the penetration of the molecule through the cell membrane to the intracellularly localized enzyme, which is important for the effectiveness of the compound in cellular models.

Purpose

It is used in pharmacological studies as a tool for selective acetylation and inactivation of COX-2 in the study of the prostaglandin signaling pathway, as well as a reference compound in the development of new generation selective cyclooxygenase inhibitors. The thioester bond with the acetoxy group on the phenolic ring and the alkynyl substituent determine the specificity of the interaction of the molecule with the active site of the human cyclooxygenase enzyme.

Storage and handling

Store in an airtight container, in a cool, dry place, protected from light and moisture, preferably at a low temperature to preserve the activity of the acetoxy group, which is prone to hydrolysis in the presence of moisture. When working with dry substances and concentrated solutions, use gloves and safety glasses, avoid inhalation of vapors and contact with skin, and work with concentrates in a fume hood.