Publications (3)5.47 Total impact
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ABSTRACT: Melanogenesis is a physiological process that results in the production of melanin pigment. However, excessive accumulations of epidermal pigmentation can cause various hyperpigmentary disorders such as, melasma and age spots. Kojic acid and hydroxylated cinnamic acid derivatives are known to inhibit tyrosinase, a key component of melanin biosynthesis. Pyronyl-acrylic acid esters 3a-i, which share structural features of kojic acid and hydroxylated cinnamic acid, were prepared and their abilities to inhibit tyrosinase and melanin production were evaluated. Of the esters synthesized, 3e and 3h, which derived from diethylene glycol moieties were found to inhibit melanin production by ca. 20% at 20 microg/ml, whereas kojic acid at 200 microg/ml inhibited melanin production by 15.8%.Bioorganic & medicinal chemistry letters 12/2008; 19(1):188-91. · 2.65 Impact Factor
Article: Synthesis and biological evaluation of a library of resveratrol analogues as inhibitors of COX-1, COX-2 and NF-kappaB.[show abstract] [hide abstract]
ABSTRACT: Resveratrol (4,3',5'-trihydroxystilbene) is a naturally occurring antioxidant that inhibits cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and the transcription factor NF-kappaB. A 78-membered library of resveratrol analogues in which the substituents on the two aryl rings and alkene were varied was synthesized using a solid-phase Wittig olefination reaction. The library contains inhibitors against all three proteins that were more potent than resveratrol itself. Preliminary structure-activity relationships were also obtained from these data that permitted the derivation of pharmacophore models for each of the three targets.Bioorganic & medicinal chemistry 06/2008; 17(3):1044-54. · 2.82 Impact Factor
Article: A photolabile backbone amide linker for the solid-phase synthesis of cyclic peptides. Cysteine-free native chemical ligation. Synthesis and biological evaluation of a library of resveratrol analogues[show abstract] [hide abstract]
ABSTRACT: A new backbone amide linker has been developed for the synthesis of cyclic and C-terminally modified peptides that permits photochemical detachment of the synthesized peptide from the solid support, thus avoiding the problems associated with acid deprotection conditions. An initial survey of known photolabile motifs for their ability to produce a linker-bound model dipeptide in high yield and their ability to undergo efficient photochemical detachment of the model dipeptide found that the 6-nitroveratryl (Nve) motif afforded the most efficient release of dipeptide. The problematic acylation of Nve-bound amino esters was solved through the development of the 2-hydroxy-4-carboxy-6-nitrobenzyl (Hcnb) linker, which utilizes an O to N transacylation to afford efficient acylation of even sterically hindered linker-bound amino esters. The Hcnb linker was found to afford high yields of amino acid loading, acylation and photolytic cleavage of model dipeptides. Attachment of the Hcnb linker to the aminoethyl TG resin permitted the solid phase synthesis of several representative cyclic peptides in high overall yield and purity. Cysteine-free Native Chemical Ligation (NCL) was studied using the photolabile Hcnb linker. Transacylation of peptide C-terminal thioesters to the Hcnb auxiliary and intramolecular O to N acyltransfer were promoted well by the electron deficient character of Hcnb in a pH 7.5 phosphate buffer. However, it needed sterically less-hindered C-terminal thioesters, and a general solution is under investigation. Resveratrol is a naturally occurring antioxidant that inhibits cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), transcription factor NF-κB, and quinine reductase-2 (QR-2). A 78-membered library of resveratrol analogues in which the substituents on the two aryl rings and the alkene were varied was synthesized using a solid-phase Wittig olefination reaction. The library contains inhibitors against all four proteins that were more potent than resveratrol itself. Preliminary structure-activity relationships were also obtained from these data that permitted the derivation of crude pharmacophore models for each of the three targets. A 27-membered library of benzanilides in which the two aromatic rings mimic the structure of bioactive resveratrols was synthesized by amide bond formation. The synthetic efforts were for the increasing molecular diversity and the observation of the aromatic rings, rotational conformation.ETD Collection for Purdue University.