133239-50-6Relevant articles and documents
Synthesis, in vitro and in vivo antimycobacterial activities of diclofenac acid hydrazones and amides
Sriram, Dharmarajan,Yogeeswari, Perumal,Devakaram, Ruth Vandana
, p. 3113 - 3118 (2006)
Various diclofenac acid hydrazones and amides were synthesized and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis. Preliminary results indicated that most of the compounds demonstrated better in vitro antimycobacterial activity (MIC: 0.0383-7.53 μM) than diclofenac (MIC: 21.10 μM) and ciprofloxacin (MIC: 9.41 μM). Among the synthesized compounds, 1-cyclopropyl-6-fluoro-8-methoxy- 7-[[N4-(2-(2-(2,6-dichlorophenylamino)phenyl)acetyl)-3-methyl]-N 1-piperazinyl]-4-oxo-1,4-dihydro-3-quinoline carboxylic acid (5d) was found to be the most active compound in vitro with MIC of 0.0383 μM and was more potent than first line antitubercular drug isoniazid (MIC: 0.1822 μM). In the in vivo animal model 5d decreased the bacterial load in lung and spleen tissues with 2.42 - and 3.66 - log 10 protections, respectively, at 25 mg/kg body weight.
Synthesis and biological activity evaluation of new thiazolidinone-diclofenac hybrid molecules
Shepeta, Yulia,Lozynskyi, Andrii,Sulyma, Marta,Nektegayev, Ihor,Grellier, Philippe,Lesyk, Roman
, p. 836 - 841 (2020)
A novel series of [2-(2,6-dichlorophenylamino)-phenyl]-acetic acid N`-3-(substituted)-4-thiazolidin-5-ylidenemethyl-hydrazide derivatives has been designed and synthesized. The structures of synthesized compounds were confirmed by their 1H NMR,
Synthesis of Novel Diclofenac Hydrazones: Molecular Docking, Anti-Inflammatory, Analgesic, and Ulcerogenic Activity
Al-Dhfyan, Abdullah,Al-Omar, Mohamed A.,Al-Tuwajiri, Hanaa M.,Alsaif, Nawaf A.,Bhat, Mashooq A.,Naglah, Ahmed M.
, (2020)
This study was aimed to design novel diclofenac hydrazones having anti-inflammatory and analgesic activity with gastric sparing effect. A new series of 2-[2-(2,6-dichloroanilino)phenyl]-N'-[(substituted phenyl) methylidene] acetohydrazide derivatives (1-14) were synthesized and evaluated for their anti-inflammatory, analgesic, and ulcerogenic activity. The compounds were identified and confirmed by elemental analysis and spectral data. During anti-inflammatory activity by carrageenan-induced paw edema method, compounds (2, 3, 7, 8, 11, and 13) were found to be most promising. Compounds 3, 8, and 13 have been found to have significant analgesic activity compared to the reference drug diclofenac in analgesic activity by both the hot plate method and acetic acid-induced writhing method. The compounds which presented highly significant anti-inflammatory and analgesic activity were further tested for their ulcerogenic activity. Compounds 3 and 8 showed maximum ulcerogenic reduction activities. Compound 8 was found to have LD50 of 168 mg/kg. Compound 8 with 3,5-dimethoxy-4-hydroxyphenyl substitution was found to be the most promising anti-inflammatory and analgesic agent with gastric sparing activity. Molecular docking of compounds was performed for COX-1/COX-2 binding site. Lead compound 8 showed better binding affinities of -9.4 kJ/mol with both COX-1 and COX-2 as compared to the standard drug, diclofenac with binding affinities of -6.6 kJ/mol and -8.1 kJ/mol for COX-1 and COX-2, respectively.
Diclofenac-Based Hydrazones and Spirothiazolidinones: Synthesis, Characterization, and Antimicrobial Properties
Kocabalkanl?, Ay?e,Cihan-üstünda?, G?k?e,Naesens, Lieve,Matarac?-Kara, Emel,Nassozi, Mebble,?apan, Gültaze
, (2017)
We report here the synthesis, structural characterization, and biological evaluation of novel diclofenac-based hydrazone (4a–f) and spirothiazolidinone (5a–f, 6a–f) derivatives designed as potential antimicrobial agents. The compounds were evaluated in vi
Cu(II) complexes of hydrazones–NSAID conjugates: synthesis, characterization and anticancer activity
Bandyopadhyay, Parbati,Basu, Soumya,Chikate, Rajeev,Chikate, Tanmayee,Kaur, Jatinder
, p. 3186 - 3202 (2020/12/22)
The hydrazones of nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac and ibuprofen are synthesized with aldehydes of pyridine and imidazole and are characterized by 1H, 13C and mass spectroscopy. Cu(II) complexes of hydrazones constructed from these ligands possess square planar geometry for bidentate diclofenac-hydrazone and tridentate ibuprofen-hydrazone conjugates with [Cu(L)2] and [Cu(L)Cl] compositions, respectively. The observed irreversible Cu(II)/Cu(I) redox couple in the range of +0.20 to +0.61 V is due to the substantial distortion in the square-planar geometry. ESR studies indicate the appreciably covalent character within M–L bonding due to extensive delocalization of electron from d x2–-y2 orbital. The hydrazone–NSAID conjugates exhibit substantial cytotoxicity against A-549, HCT-116 and MDA-MB-231 cancer cell lines with ibuprofen-imidazole-hydrazone ligand possessing the lowest IC50 (2.26 μM) amongst the synthesized NSAID-conjugates. Interestingly, its Cu(II) complex also displays excellent anticancer activity against MDA-MB- 231 with IC50 value of 3.58 μM. Such a feature may be ascribed to the synergistic association of Cu(II)–NSAID–hydrazone linkage. Thus, conjugation of NSAID with hydrazone and its complexation with a bioactive metal ion may be regarded as a potential strategy for designing of non-platinum anticancer agents.
Diclofenac 1,3,4-oxadiazole derivatives; biology-oriented drug synthesis (BIODS) in search of better non-steroidal, non-acid antiinflammatory agents
Shah, Shazia,Arshia,Kazmi, Nida Siraj,Jabeen, Almas,Khan, Khalid Mohammed,Raza, Abeer,Faheem, Aisha,Dastagir, Nida,Ahmed, Tariq,Ahmed, Shakil,Perveen, Shahnaz
, p. 674 - 687 (2018/11/21)
Background: Inflammation is defined as the response of immune system cells to damaged or injured tissues. The major symptoms of inflammation include increased blood flow, cellular influx, edema, elevated cellular metabolism, reactive oxygen species (ROS) nitric oxide (NO) and vasodilation. This normally protective mechanism against harmful agents when this normal mechanism becomes dysregulated that can cause serious illnesses including ulcerative colitis, Crohn’s disease, rheumatoid arthritis, osteoarthritis, sepsis, and chronic pulmonary inflammation. Method: In this study synthetic transformations on diclofenac were carried out in search of better non-steroidal antiinflammatory drugs (NSAIDs), non-acidic, antiinflammatory agents. For this purpose diclofenac derivatives (2-20) were synthesized from diclofenac (1). All derivatives (2-20) and parent diclofenac (1) were evaluated for their antiinflammatory effect using different parameters including suppression of intracellular reactive oxygen species (ROS), produced by whole blood phagocytes, produced by neutrophils, and inhibition of nitric oxide (NO) production from J774.2 macrophages. The most active compound also evaluated for cytotoxicity activity. Results: Diclofenac (1) inhibited the ROS with an IC of 3.9 ± 2.8, 1.2 ± 0.0 μg/mL respectively 50 and inhibited NO with an IC50 of 30.01 ± 0.01 μg/mL. Among its derivatives 4, 5, 11, 16, and 20, showed better antiinflammatory potential. The compound 5 was found to be the most potent inhibitor of intracellular ROS as well as NO with IC50 values of 1.9 ± 0.9, 1.7 ± 0.4 μg/mL respectively and 7.13 ± 1.0 μg/mL, respectively, and showed good inhibitory activity than parent diclofenac. The most active compounds were tested for their toxic effect on NIH-3T3 cells where all compounds were found to be non-toxic compared to the standard cytotoxic drug cyclohexamide. Conclusion: Five derivatives were found to be active. Compound 5 was found to be the most potent inhibitor of ROS and NO compared to parent diclofenac 1 and standard drugs ibuprofen and L-NMMA, respectively. The most active compounds 1, 4, 5, 11 and 20 were found to be non-toxic on NIH-3T3 cells. Compound 4, 5, and 20 also showed good antiinflammatory potential, compound 11 and 16 showed moderate and low level of inhibition, respectively.
Design, synthesis and QSAR studies on a series of 2, 5-disubstituted-1,3,4-oxadiazole derivatives of diclofenac and naproxen for analgesic and anti-inflammatory activity
Ilango, Kaliappan,Valentina, Parthiban,Kumar, Gajendra,Dixit, Dushyant,Nilewar, Shrikant,Kathiravan, Muthu K.
, p. 753 - 763 (2015/12/01)
A series of twenty molecules belonging to 2, 5-disubstituted-1, 3, 4-oxadiazole derivatives of Diclofenac and Naproxen were designed, synthesized and their structures were confirmed by spectroscopy. The target compounds were evaluated for anti-inflammator
Synthesis, pharmacological screening and in silico studies of new class of Diclofenac analogues as a promising anti-inflammatory agents
Palkar, Mahesh B.,Singhai, Anuj S.,Ronad, Pradeepkumar M.,Vishwanathswamy,Boreddy, Thippeswamy S.,Veerapur, Veeresh P.,Shaikh, Mahamadhanif S.,Rane, Rajesh A.,Karpoormath, Rajshekhar
, p. 2855 - 2866 (2014/05/06)
A novel series of 5-[2-(2,6-dichlorophenylamino)benzyl]-3-(substituted)-1, 3,4-oxadiazol-2(3H)-thione (4a-k) derivatives have been synthesized by the Mannich reaction of 5-[2-(2,6-dichlorophenylamino)benzyl]-1,3,4-oxadiazol-2(3H)- thione (3) with an appropriately substituted primary/secondary amines, in the presence of formaldehyde and absolute ethanol. Structures of these novel compounds were characterized on the basis of physicochemical, spectral and elemental analysis. The title compounds (4a-k) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 10 mg/kg b.w. Compound 4k exhibited the most promising and significant anti-inflammatory profile while compounds 4a, 4d, 4e, 4i, and 4j showed moderate to good inhibitory activity at 2nd and 4th h, respectively. These compounds were also found to have considerable analgesic activity (acetic acid induced writhing model) and antipyretic activity (yeast induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. Compounds that displayed promising anti-inflammatory profile were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 4a, 4e, 4g and 4k exhibited effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of the binding affinity, docking studies were performed using Molegro Virtual Docker (MVD-2013, 6.0) for those compounds, which showed good anti-inflammatory activity. It was observed that the binding affinities calculated were in agreement with the IC 50 values.
PHTHALIMIDE DERIVATIVES OF NON-STEROIDAL ANTI-INFLAMMATORY COMPOUNDS AND/OR TNF- MODULATORS, METHOD FOR PRODUCING SAME, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND USES THEREOF FOR THE TREATMENT OF INFLAMMATORY DISEASES
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Page/Page column 34, (2012/03/08)
The present invention relates to phthalimide derivatives of non-steroidal and/or TNF-α modulating anti-inflammatory compounds as well as the process of obtaining the so-called derivatives, pharmaceutical compositions containing such derivatives and their uses, including use in the treatment of inflammatory diseases, especially those related to chronic inflammatory processes, such as rheumatoid arthritis and intestinal inflammatory diseases (for instance, Chron's disease) and the use of the referred to pharmaceutical compositions as antipyretic, analgesic and platelet antiaggregating medications.
PHTHALIMIDE DERIVATIVES OF NON-STEROIDAL ANTI-INFLAMMATORY COMPOUNDS AND/OR TNF-ALPHA MODULATORS, METHOD FOR PRODUCING SAME, PHARMACEUTICAL COMPOSITIONS CONTAINING SAME AND USES THEREOF FOR THE TREATMENT OF INFLAMMATORY DISEASES
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Page/Page column 46, (2012/05/20)
The present invention relates to phthalimide derivatives of non-steroidal and/or TNF-α modulating anti-inflammatory compounds as well as the process of obtaining the so-called derivatives, pharmaceutical compositions containing such derivatives and their uses, including use in the treatment of inflammatory diseases, especially those related to chronic inflammatory processes, such as rheumatoid arthritis and intestinal inflammatory diseases (for instance, Chron's disease) and the use of the referred to pharmaceutical compositions as antipyretic, analgesic and platelet antiaggregating medications.
