2-hydroxycinnamic-acid and coumarin

The o-hydroxycinnamic derivatives represent efficient caged compounds that can realize quantification of delivery upon uncaging, but there has been lack of time-resolved and mechanistic studies. We used time-resolved infrared (TRIR) spectroscopy to investigate the photochemical uncaging dynamics of the prototype o-hydroxycinnamic compound, (E)-3-(2-hydroxyphenyl)-acrylic acid ethyl ester (HAAEE), leading to coumarin and ethanol upon uncaging. Taking advantage of the specific vibrational marker bands and the IR discerning capability, we have identified and distinguished two key intermediate species, the cis-isomers of HAAEE and the tetrahedral intermediate, in the transient infrared spectra, thus providing clear spectral evidence to support the intramolecular nucleophilic addition mechanism following the trans-cis photoisomerization. Moreover, the product yields of coumarin upon uncaging were observed to be greatly affected by the solvent polarity, suppressed in CH2Cl2 but enhanced in D2O/CH3CN with the increasing volume ratio of D2O. The highly solvent-dependent behavior indicates E1 elimination of the tetrahedral intermediate to give rise to the final uncaging product coumarin. The photorelease rate of coumarin was directly characterized from TRIR (3.6 × 10(6) s(-1)), revealing the promising application of such o-hydroxycinnamic compound in producing fast alcohol jumps. The TRIR results provide the first time-resolved detection and thus offer direct dynamical information about this photochemical uncaging reaction.

Topics: Coumaric Acids; Coumarins; Ethanol; Molecular Structure; Photochemical Processes; Spectrophotometry, Infrared; Time Factors; Ultraviolet Rays

The inhibition of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1) with (thio)coumarins has been recently reported (Maresca et al., J. Am. Chem. Soc. 2009, 131, 3057). Here we demonstrate that a series of γ- and δ-(thio)lactones also act as mechanism based, prodrug type CA inhibitors, similar to the (thio)coumarins. Through the esterase activity of CA, these compounds are hydrolyzed in situ to the corresponding hydroxy/keto/mercapto acids which thereafter act as inhibitors. CA isoforms I and IX were efficiently inhibited by simple such compounds, with K(I)s in the range of 0.92-19.1μM, whereas CA II was not inhibited at all. Isoform-selective CA inhibitors which spare the ubiquitous off-target CA II may have interesting applications for example for selectively inhibiting the tumor-associated CA IX, a validated anticancer target.

Topics: Antineoplastic Agents; Carbonic Anhydrase Inhibitors; Chemistry, Pharmaceutical; Coumarins; Drug Design; Enzyme Inhibitors; Humans; Kinetics; Lactones; Models, Chemical; Neoplasms; Prodrugs; Protein Isoforms

We synthesized all of the monomethoxycoumarins, 5-alkoxycoumarins and their derivatives, and investigated their nematicidal activity against the phytopathogenic nematode, Bursaphelenchus xylophilus. Among the compounds, 5-ethoxycoumarin showed the highest nematicidal activity. Furthermore, 5-ethoxycoumarin was comparatively harmless against both the brine shrimps, Artemia salina, and the Japanese killifish, Oryzias latipes.

Topics: Animals; Antinematodal Agents; Artemia; Biological Assay; Chemistry, Pharmaceutical; Coumarins; Drug Design; Hydrolysis; Models, Chemical; Nematoda; Oryzias; Structure-Activity Relationship