Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies

Khatri, Chetan K.; Indalkar, Krishna S.; Patil, Chandragouda R.; Goyal, Sameer N.; Chaturbhuj, Ganesh U.

doi:10.1016/j.bmcl.2017.02.076

Cited by 20 publications

(12 citation statements)

References 22 publications

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“…Khatri and colleagues [ 73 ] conducted a similar study, using in vitro, in vivo, and in silico studies with 2-phenyl-4,5,6,7-tetrahydro[ b ]benzothiophene derivatives as selective COX-2 inhibitors. Compounds ( 29a–d ) ( Figure 6 ) were revealed as selective COX-2 inhibitors, presenting IC 50 values in the 0.31–1.40 µM range.…”

Section: The Role Of Thiophene Derivatives In Inflammationmentioning

confidence: 99%

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

et al. 2021

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Rheumatoid arthritis, arthrosis and gout, among other chronic inflammatory diseases are public health problems and represent major therapeutic challenges. Non-steroidal anti-inflammatory drugs (NSAIDs) are the most prescribed clinical treatments, despite their severe side effects and their exclusive action in improving symptoms, without effectively promoting the cure. However, recent advances in the fields of pharmacology, medicinal chemistry, and chemoinformatics have provided valuable information and opportunities for development of new anti-inflammatory drug candidates. For drug design and discovery, thiophene derivatives are privileged structures. Thiophene-based compounds, like the commercial drugs Tinoridine and Tiaprofenic acid, are known for their anti-inflammatory properties. The present review provides an update on the role of thiophene-based derivatives in inflammation. Studies on mechanisms of action, interactions with receptors (especially against cyclooxygenase (COX) and lipoxygenase (LOX)), and structure-activity relationships are also presented and discussed. The results demonstrate the importance of thiophene-based compounds as privileged structures for the design and discovery of novel anti-inflammatory agents. The studies reveal important structural characteristics. The presence of carboxylic acids, esters, amines, and amides, as well as methyl and methoxy groups, has been frequently described, and highlights the importance of these groups for anti-inflammatory activity and biological target recognition, especially for inhibition of COX and LOX enzymes.

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Section: The Role Of Thiophene Derivatives In Inflammationmentioning

confidence: 99%

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

et al. 2021

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“…Recently, several compounds have been synthesised and evaluated as selective COX-2 inhibitors. Their common structural features involve the presence of two adjoining aryl rings attached to a central heterocyclic moiety (V-shape) with the possibility of introduction of a linker, either an ester 11 or an amide 12 , 13 , between one of the aryl rings and the central heterocycle.…”

Section: Introductionmentioning

confidence: 99%

“…In continuation of our previous study, herein, we made further modifications to our previous successfully designed anti-inflammatory quinazolinones ( I ) ( Figure 1 ), in order to increase their selectivity towards COX-2 inhibition 13 . In our current design, we kept the following: (a) the 2,3 diaryl-heterocyclic moiety (V-shape) to maintain the common structural integrity of selective COX-2 inhibitors 10 , 11 , 13 , (b) quinazolinone as the central heterocyclic ring due to its remarkable anti-inflammatory and analgesic activities 13 , 14 , and (c) the aryl ring at position 3 connected via an amide linker which may potentiate target interactions. Additionally, the introduction of the amide linker to the compounds allows for a bulkier structure, and thus, more favourable for COX-2 active site entry, which is approximately 20% larger than the COX-1 active site 12 , 13 .…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities

Sakr

Rezq

Ibrahim

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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Novel quinazolinones conjugated with indole acetamide (4a–c) , ibuprofen ( 7a–e), or thioacetohydrazide ( 13a,b, and 14a-d ) were designed to increase COX-2 selectivity. The three synthesised series exhibited superior COX-2 selectivity compared with the previously reported quinazolinones and their NSAID analogue and had equipotent COX-2 selectivity as celecoxib. Compared with celecoxib, 4 b , 7c , and 13 b showed similar anti-inflammatory activity in vivo , while 13 b and 14a showed superior inhibition of the inflammatory mediator nitric oxide, and 7 showed greater antioxidant potential in macrophages cells. Moreover, all selected compounds showed improved analgesic activity and 13 b completely abolished the pain response. Additionally, compound 4a showed anticancer activity in tested cell lines HCT116, HT29, and HCA7. Docking results were consistent with COX-1/2 enzyme assay results. In silico studies suggest their high oral bioavailability. The overall findings for compounds ( 4a,b, 7c, 13 b, and 14c ) support their potential role as anti-inflammatory agents.

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“…Side effects include gastrointestinal toxicity such as gastro-duodenal perforations, ulcers and bleeding, ascribed to the inhibition of cyclooxygenase-1 (COX-1). Thus, selective inhibitors of cyclooxygenase-2 (COX-2) were synthesised in an attempt to decrease these side effects [2][3][4][5][6] . Physicians would prescribe gastro-protective agents with a conventional NSAID, prior to the introduction of the COX-2 selective inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity

Bhat

Al-Omar

Alsaif

et al. 2020

Journal of Enzyme Inhibition and Medicinal Chemistry

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A new series of N 0-(substituted phenyl)-2-(1-(4-(methylsulfinyl) benzylidene)À5-fluoro-2-methyl-1H-inden-3yl) acetohydrazide derivatives (1-25) were prepared in good yields in an efficient manner. All the compounds were fully characterised by the elemental analysis and spectral data. Synthesised compounds were evaluated for antioxidant activity by DPPH method. Compounds 7 (R ¼ 3-methoxyphenyl), 3 (R ¼ 4dimethylaminophenyl) and 23 (R ¼ 2,4,5-trimethoxy phenyl) substitutions were found to be having highly potent antioxidant activity. Compound 3, with para dimethylaminophenyl substitution was found to be having highest antioxidant activity. It was further evaluated in vivo for various analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibitory activity in different animal models. Lead compound 3 was found to be significant anti-inflammatory and analgesic agent. It was also evaluated for ulcerogenic activity and demonstrated significant ulcerogenic reduction activity in ethanol and indomethacin model. The LD 50 of compound 3 was found to be 131 mg/kg. The animals treated with compound 3 prior to cisplatin treatment resulted in a significant reduction in COX-2 protein expression when compared to cisplatin-treated group. Sulindac derivative with para dimethylaminophenyl substitution was found to be the most potent antioxidant, anti-inflammatory and analgesic agent as well as with significant gastric sparing activity as compared to standard drug sulindac. Compound 3 significantly downregulated liver tissue COX-2 gene expression.

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Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies

Cited by 20 publications

References 22 publications

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Thiophene-Based Compounds with Potential Anti-Inflammatory Activity

Design and synthesis of novel quinazolinones conjugated ibuprofen, indole acetamide, or thioacetohydrazide as selective COX-2 inhibitors: anti-inflammatory, analgesic and anticancer activities

Novel sulindac derivatives: synthesis, characterisation, evaluation of antioxidant, analgesic, anti-inflammatory, ulcerogenic and COX-2 inhibition activity

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