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.
Peptide conjugates of a nonsteroidal anti-inflammatory drug as supramolecular gelators: Synthesis, characterization, and biological studies
Roy, Rajdip,Deb, Jolly,Jana, Siddhartha Sankar,Dastidar, Parthasarathi
, p. 3196 - 3206 (2014)
Indomethacin (IND), which is a well-known nonsteroidal anti-inflammatory drug (NSAID), was conjugated with various naturally occurring amino acids. Most of these bioconjugates were capable of gelling pure water, a solution of NaCl (0.9 wt%), and phosphate
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.
Multidrug-Containing, Salt-Based, Injectable Supramolecular Gels for Self-Delivery, Cell Imaging and Other Materials Applications
Roy, Rajdip,Dastidar, Parthasarathi
, p. 14929 - 14939 (2016)
Both molecular and crystal-engineering approaches were exploited to synthesize a new class of multidrug-containing supramolecular gelators. A well-known nonsteroidal anti-inflammatory drug, namely, indomethacin, was conjugated with six different l-amino a
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
COX-2 enzyme targeting phthalocyanine indometacin complex as well as preparation method and application thereof
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Paragraph 0010; 0019, (2021/01/24)
The invention discloses a COX-2 enzyme targeting phthalocyanine indometacin complex as well as a preparation method and application thereof, and the preparation method comprises the following steps: by taking 3-nitro phthalonitrile as an original raw mate
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.
Salt metathesis for developing injectable supramolecular metallohydrogelators as a multi-drug-self-delivery system
Roy, Rajdip,Bhagyalalitha, Meduri,Choudhury, Pritam,Dastidar, Parthasarathi
supporting information, p. 13811 - 13814 (2016/12/03)
Salt metathesis has been exploited to generate a series of non-steroidal anti-inflammatory drug (NSAID) based Zn(ii) metallohydrogels displaying both anti-inflammatory and anti-bacterial properties. Relatively low cytotoxicity, rheoreversibility and injec
Therapeutic compound-fatty acid conjugates
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Page column 7, (2010/01/30)
The present invention provides therapeutic conjugates which comprise a therapeutic compound bound to one to three acyl groups derived from fatty acids. The therapeutic compounds are preferably non-steroidal anti-infiammatory agents which include a carboxylic acid group. The compounds involve the use of tromethamine or ethanolamine derivative to link the acyl groups derived from fatty acids to the therapeutic compounds.
Low molecular weight proteins as carriers for renal drug targeting. Preparation of drug-protein conjugates and drug-spacer derivatives and their catabolism in renal cortex homogenates and lysosomal lysates
Franssen,Koiter,Kuipers,Bruins,Moolenaar,De Zeeuw,Kruizinga,Kellogg,Meijer
, p. 1246 - 1259 (2007/10/02)
Low molecular weight proteins (LMWPs) are known to be reabsorbed and catabolized primarily by the proximal tubular cells of the kidneys. As such, LMWPs might serve as drug carriers that release drugs site-specifically in the kidney. We tested this concept in vitro by coupling different drugs to the LMWP lysozyme both directly (amide bond) and via different spacers: oligopeptides (amide bond), (poly-)α-hydroxy acids (ester bond), and a pH sensitive cis-aconityl spacer (amide bond). The capability of the kidney to release the parent drug from such drug-spacer derivatives and drug-LMWP conjugates by enzymatic or chemical hydrolysis of the bond was tested by incubation experiments in renal cortex homogenates and lysosomal lysates. Directly coupled conjugates of terminal carboxyl group containing drugs and lysozyme were catabolized to single amino acids, but did not result in release of the parent drug. The amide bond between the drug and the final amino acid (lysine) appeared to be stable in the incubation milieu. Different oligopeptide spacers coupled to the drugs showed similar results: the oligopeptide itself was cleaved but the amide bond between the drug and different single amino acids remained untouched. Only amide bonds of derivatives of carboxylic drugs with peptide structures themselves were cleaved. Some of the directly coupled conjugates of terminal amino drugs and oligopeptides showed clear release of the parent drug whereas others were stable. Terminal amino drugs were rapidly released from an acid-sensitive cis-aconityl spacer. Terminal carboxyl group containing drugs were enzymatically released from their glycolic and lactic ester spacers at different rates. These kinds of drugs were also released as parent drug from LMWP conjugates with ester spacers like L-lactic acid. Increasing spacer length by intercalating a tetra(L-lactic acid) molecule between the drug and the protein further increased the extent and rate of drug release, indicating increased accessability of the bond to the enzymes. Terminal amino group containing drugs were rapidly generated as parent drug from LMWP conjugates using an acid-sensitive spacer. In addition the conjugates were found to be adequately stable in plasma, considering their rapid clearance from the bloodstream. It is concluded that LMWPs may indeed be of use as carriers for specific renal delivery of drugs, since renal cortex homogenates and lysosomal lysates are able to catabolize the protein and generate the parent drug from drug-LMWP conjugates bearing suitable spacers. The option of enzymatic release is limited by the narrow specificity of the lysosomal enzymes. This has profound implications for the synthesis of suitable conjugates, since the nature of the drug itself, the type of bond and also spacer length largely determine whether release of the parent drug will occur. Tailor-made spacers containing the correct mode of attachment and the right spacer length are required for this option. Chemical hydrolysis using acid-sensitive linkers, is suggested as a viable alternative approach.
