Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX

Omar, Yasser M.; Abdu-Allah, Hajjaj H.M.; Abdel-Moty, Samia G.

doi:10.1016/j.bioorg.2018.06.036

Cited by 64 publications

(42 citation statements)

References 26 publications

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“…The structure of MMPT has been considered as a “pharmacophore model” for further optimization 21 , and a set of structural requirements were proposed: an unsubstituted N3 atom in the main core, a C5 p -substituted-arylidene moiety, and a C2-arylamino fragment which can be substituted in different positions 18 . Moreover, MMPT analogs were found to exert anti-inflammatory activity through COX/LOX inhibition 48 . Other different activities of the related compounds are also being studied.…”

Section: Introductionmentioning

confidence: 99%

Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one

Szychowski

Kaminskyy

Leja

et al. 2019

Sci Rep

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4-thiazolidinones, which are privileged structures in medicinal chemistry, comprise the well-known class of heterocycles and are a source of new drug-like compounds. Undoubtedly, the 5-bulky-substituted-2,4-thiazolidinediones - a class of antihyperglycemic glitazones, which are peroxisome proliferator-activated receptor gamma (PPARγ) agonists, are the most described group among them. As there are various chemically distinct 4-thiazolidinones, different subtypes have been selected for studies; however, their main pharmacological profiles are similar. The aim of this study was to evaluate the anticancer activity of 5 Z -(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one (Les-236) in four human cancer cell lines, A549, SCC-15, SH-SY5Y, and CACO-2, and investigate its impact on the production of reactive oxygen species (ROS) and the apoptotic process as well as cytotoxicity and metabolism in these cell lines. The cell lines were exposed to increasing concentrations (1 nM to 100 µM) of the studied compound for 6, 24, and 48 h, and later, ROS production, cell viability, caspase-3 activity, and cell metabolism were examined. The obtained results showed that the studied compound decreased the production of ROS, increased the release of lactate dehydrogenase, and decreased cell metabolism/proliferation in all the five cell lines at micromolar concentrations. Interestingly, over a wide range of concentrations (from 1 nM to 100 µM), Les-236 was able to increase the activity of caspase-3 in BJ (after 6 h of exposure), A549, CACO-2, and SCC-15 (after 48 h of exposure) cell lines which could be an effect of the activation of PPARγ-dependent pathways.

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Section: Introductionmentioning

confidence: 99%

Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one

Szychowski

Kaminskyy

Leja

et al. 2019

Sci Rep

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“…Recently, 1,3,4-thiadiazole derivatives exhibited biological effects such as antitumor, anti-inflammatory, antioxidant, and antimicrobial activity [8][9][10]. In the present study, a new derivative of HSP was synthesized by reacting with hydrazine derivatives to form the respective analogs.…”

Section: Introductionmentioning

confidence: 96%

Design, Synthesis, Docking, Antitumor Screening, and Absorption, Distribution, Metabolism, and Excretion Prediction of New Hesperdin Derivative

Al-Shmgani

Shakir

Naser

et al. 2019

Asian J Pharm Clin Res

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Objective: Hesperidin (HSP) is a pharmacologically active organic compound found in citrus fruits and peppermint. We synthesized a new HSP derivative by reacting it with 5-Amino-1,3,4-thiadiazole-2-thiol in acetic acid. Methods: This compound was characterized by Fourier-transform infrared, proton nuclear magnetic resonance, and electron impact mass spectra. A molecular docking study explores the predicted binding of the compound and its possible mode of action. Bioavailability, site of absorption, drug mimic, and topological polar surface was predicted using absorption, distribution, metabolism, and excretion (ADME) studies. Results: The docking study predicts that the new compound binds to the active sites of Aurora-B and the MST3 pocket and has good ADME properties. Moreover, the thiazole ring and the presence of the electron releasing groups and hydrogen bond interaction with amino acid residues within the active sites play an important role in enhancing the antioxidant activity. Conclusion: In the present study, a new HSP derivative has been synthesized and characterized successfully and a theoretically promising antioxidant and anticytotoxic active agent introduced. We have shown the detailed binding analysis of 1,3,4-thiadiazol and hydrogen bonds with the inhibitor binding cavity of Aurora B and MST3. This could provide the development of some effective compounds against different diseases.

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“…23 However, other fascinating biological effects are as cathepsin B inhibitors, 24 as allosteric modulators binding at secondary binding site of biomolecules, 25 non-ATP competitive GSK-3 inhibitors 26 and as dual 5-lipoxygenase and cyclooxygenase inhibitors. 27 1,2,4-thiadiazoles have been synthesized by various methods, like copper-catalyzed reaction of amidine hydrochlorides with isothiocyanates, 28 from aryl nitriles in 1-butyl-3-methylimidazolium bromide, 29 molecular iodine catalyzed N─S bond formation, 30 copper-catalyzed aerobic oxidative annulation, 31 and electrochemical intermolecular dehydrogenative S─N coupling. 32 Despite these interesting reports for synthesis of these moieties, visible light promoted methods for synthesis of 1,2,4-thiadiazoles remains a relatively unexplored area.…”

Section: Introductionmentioning

confidence: 99%

Visible light promoted formation of N─S bond by photocatalyst Eosin Y

Verma

Srivastava

Tiwari

et al. 2020

Journal of Heterocyclic Chem

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A novel efficient protocol for the synthesis of 5‐imino‐1,2,4‐thiadiazole motif in open air and visible light has been reported. The reaction involves Eosin Y as photocatalyst which is a cost‐effective organic dye. The designed protocol represents a novel, mild, metal free, green strategy for the construction of 1,2,4‐thiadiazole nucleus by intramolecular cyclization via N─S bond formation. The reaction has been carried out under visible light exposure in ethanol: water (4:1) mixture using 2‐aminopyridine and isocyanate as reactants.

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Synthesis, biological evaluation and docking study of 1,3,4-thiadiazole-thiazolidinone hybrids as anti-inflammatory agents with dual inhibition of COX-2 and 15-LOX

Cited by 64 publications

References 26 publications

Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one

Anticancer properties of 5Z-(4-fluorobenzylidene)-2-(4-hydroxyphenylamino)-thiazol-4-one

Design, Synthesis, Docking, Antitumor Screening, and Absorption, Distribution, Metabolism, and Excretion Prediction of New Hesperdin Derivative

Visible light promoted formation of N─S bond by photocatalyst Eosin Y

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