Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase

Sinha, Sanjib; Manju, S. L.; Doble, Mukesh

doi:10.1021/acsmedchemlett.9b00193

Cited by 27 publications

(15 citation statements)

References 25 publications

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“…Chalcone derivatives showed good antiviral activity ( Sinha, et al, 2019 ). For example, compound 7 ( Figure 4 ) showed 55.6, 71.2 and 92.4% of curative, protective, and inactivating activities against TMV, respectively.…”

Section: Antiviral Active Compoundsmentioning

confidence: 99%

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

et al. 2022

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Plant virus diseases, also known as “plant cancers”, cause serious harm to the agriculture of the world and huge economic losses every year. Antiviral agents are one of the most effective ways to control plant virus diseases. Ningnanmycin is currently the most successful anti-plant virus agent, but its field control effect is not ideal due to its instability. In recent years, great progress has been made in the research and development of antiviral agents, the mainstream research direction is to obtain antiviral agents or lead compounds based on structural modification of natural products. However, no antiviral agent has been able to completely inhibit plant viruses. Therefore, the development of highly effective antiviral agents still faces enormous challenges. Therefore, we reviewed the recent research progress of anti-plant virus agents based on natural products in the past decade, and discussed their structure-activity relationship (SAR) and mechanism of action. It is hoped that this review can provide new inspiration for the discovery and mechanism of action of novel antiviral agents.

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Section: Antiviral Active Compoundsmentioning

confidence: 99%

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

et al. 2022

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“…LTs are thought to be crucial mediators of allergy and in ammatory diseases [18,19] . Until now, the only approved treatment for asthma is zileuton, a 5-LOX inhibitor, but its side effects include hepatotoxicity and poor pharmacokinetics [17] .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and biological evaluation of novel 2- (indole arylamide) benzoic acid analogs as dual COX-2 / 5-LOX inhibitors

et al. 2022

Preprint

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Recently, the drug discovery paradigm has evolved from single-target inhibition to a multi-target design concept. This study designed, synthesized, and evaluated a series of novel 2-(indole arylamide) benzoic acid analogs for their in vivo anti-inflammatory properties. Compounds 7f and 7n showed significant anti-inflammatory activity in a xylene-induced mouse model of auricular edema. Furthermore, 7f and 7n exhibited moderate COX-2 inhibitory activity (IC50 = 537 and 321.5 nM) than celecoxib (IC50 = 10.04 nM) in vitro, among which 7n had higher COX-2 selectivity activity (selectivity index (COX-1/COX-2) = 7.89) and moderate 5-LOX inhibitory activity (IC50 = 222.1 nM). Compared to zileuton (IC50 = 36.46 nM), compound 7f was identified as the most potent 5-LOX inhibitor (IC50 = 77.37 nM). According to the biological results, compounds 7f and 7n have better inhibitory activities on the production of NO and PGE2 in LPS-induced RAW 264.7 cell macrophages than celecoxib and indomethacin. As demonstrated by docking studies, 7f and 7n have stronger interactions with key residues in the active pocket of COX-1 or COX-2, which is consistent with the activity results. Based on these results, further research into safer and more effective anti-inflammatory drugs might be possible using 2-(indole arylamide) benzoic acid analogs.

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“…Thiazole–chalcone hybrids have been previously reported with promising antimicrobial [ 58 ], anticancer [ 24 ] and lipoxygenase (5-LOX) inhibitory [ 59 ] activities. In view of the above facts, we designed, synthesized and evaluated the antitubercular, antiproliferative and cytotoxic activities of 20 novel thiazole–chalcone hybrids ( 1 – 20 ) containing biologically active thiazole and chalcone pharmacophores in order to find novel lead molecules with improved biological activities ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

Kasetti

Singhvi

Nagasuri³

et al. 2021

Molecules

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Compounds bearing thiazole and chalcone pharmacophores have been reported to possess excellent antitubercular and anticancer activities. In view of this, we designed, synthesized and characterized a novel series of thiazole−chalcone hybrids (1–20) and further evaluated them for antitubercular and antiproliferative activities by employing standard protocols. Among the twenty compounds, chalcones 12 and 7, containing 2,4-difluorophenyl and 2,4-dichlorophenyl groups, showed potential antitubercular activity higher than the standard pyrazinamide (MIC = 25.34 µM) with MICs of 2.43 and 4.41 µM, respectively. Chalcone 20 containing heteroaryl 2-thiazolyl moiety exhibited promising antiproliferative activity against the prostate cancer cell line (DU-145), higher than the standard methotrexate (IC50 = 11 ± 1 µM) with an IC50 value of 6.86 ± 1 µM. Furthermore, cytotoxicity studies of these compounds against normal human liver cell lines (L02) revealed that the target molecules were comparatively less selective against L02. Additional computational studies using AutoDock predicted the key binding interactions responsible for the activity and the SwissADME tool computed the in silico drug likeliness properties. The lead compounds generated through this study, create a way for the optimization and development of novel drugs against tuberculosis infections and prostate cancer.

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Chalcone-Thiazole Hybrids: Rational Design, Synthesis, and Lead Identification against 5-Lipoxygenase

Cited by 27 publications

References 25 publications

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

Recent Research Progress: Discovery of Anti-Plant Virus Agents Based on Natural Scaffold

Design, synthesis and biological evaluation of novel 2- (indole arylamide) benzoic acid analogs as dual COX-2 / 5-LOX inhibitors

Thiazole–Chalcone Hybrids as Prospective Antitubercular and Antiproliferative Agents: Design, Synthesis, Biological, Molecular Docking Studies and In Silico ADME Evaluation

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