104425-42-5Relevant articles and documents
Live-Cell Protein Sulfonylation Based on Proximity-driven N-Sulfonyl Pyridone Chemistry
Matsuo, Kazuya,Nishikawa, Yuki,Masuda, Marie,Hamachi, Itaru
, p. 659 - 662 (2018)
The development of bioorthogonal approaches for labeling of endogenous proteins under the multimolecular crowding conditions of live cells is highly desirable for the analysis and engineering of proteins without using genetic manipulation. N-Sulfonyl pyridone (SP) is reported as a new reactive group for protein sulfonylation. The ligand-directed SP chemistry was able to modify not only purified proteins in vitro, but also endogenous ones on the surface of and inside live cells selectively and rapidly, which allowed to convert endogenous proteins to FRET-based biosensors in situ.
Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase
Raji, Idris,Yadudu, Fatima,Janeira, Emily,Fathi, Shaghayegh,Szymczak, Lindsey,Kornacki, James Richard,Komatsu, Kensei,Li, Jian-Dong,Mrksich, Milan,Oyelere, Adegboyega K.
, p. 1202 - 1218 (2017)
We herein disclose a series of compounds with potent inhibitory activities towards histone deacetylases (HDAC) and cyclooxygenases (COX). These compounds potently inhibited the growth of cancer cell lines consistent with their anti-COX and anti-HDAC activities. While compound 2b showed comparable level of COX-2 selectivity as celecoxib, compound 11b outperformed indomethacin in terms of selectivity towards COX-2 relative to COX-1. An important observation with our lead compounds (2b, 8, 11b, and 17b) is their enhanced cytotoxicity towards androgen dependent prostate cancer cell line (LNCaP) relative to androgen independent prostate cancer cell line (DU-145). Interestingly, compounds 2b and 17b arrested the cell cycle progression of LNCaP in the S-phase, while compound 8 showed a G0/G1 arrest, similar to SAHA. Relative to SAHA, these compounds displayed tumor-selective cytotoxicity as they have low anti-proliferative activity towards healthy cells (VERO); an attribute that makes them attractive candidates for drug development.
A novel zinc phthalocyanine-indometacin photosensitizer with “Three-in-one” cyclooxygenase-2-driven dual targeting and aggregation inhibition for high-efficient anticancer therapy
Chen, Juanjuan,Huang, Kunshan,Xue, Jinping,Yan, Meiqi,Zhang, Han
, (2021/12/07)
Photodynamic therapy, during which nontoxic photosensitizers can be photo-activated to generate cytotoxic reactive oxygen species, has attracted great interest. However, the strong aggregation and poor tumor targeting of photosensitizers, the short action
Design and Synthesis of Novel Nonsteroidal Anti-Inflammatory Drugs and Carbonic Anhydrase Inhibitors Hybrids (NSAIDs-CAIs) for the Treatment of Rheumatoid Arthritis
Bua, Silvia,Di Cesare Mannelli, Lorenzo,Vullo, Daniela,Ghelardini, Carla,Bartolucci, Gianluca,Scozzafava, Andrea,Supuran, Claudiu T.,Carta, Fabrizio
, p. 1159 - 1170 (2017/02/19)
We report the synthesis of a series of hybrid compounds incorporating 6- and 7-substituted coumarins (carbonic anhydrase, CA inhibitors) derivatized with clinically used NSAIDs (indomethacin, sulindac, ketoprofen, ibuprofen, diclofenac, ketorolac, etc., cyclooxygenase inhibitors) as agents for the management of rheumatoid arthritis (RA). Most compounds were effective in inhibiting the RA overexpressed hCA IX and XII, with KI values in the low nanomolar-subnanomolar ranges. The antihyperalgesic activity of such compounds was assessed by means of the paw-pressure and incapacitance tests using an in vivo RA model. Among all tested compounds, the 7-coumarine hybrid with ibuprofen showed potent and persistent antihyperalgesic effect up to 60 min after administration.
