Novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety: Anti-inflammatory activity on mammalian macrophages by regulating intracellular PI3K pathway, and molecular docking study

Efeoglu, Cagla; Yetkin, Derya; Nural, Yahya; Ece, Abdulilah; Seferoğlu, Zeynel; Ayaz, Furkan

doi:10.1016/j.molstruc.2022.133284

Cited by 18 publications

(7 citation statements)

References 66 publications

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“…[22] Due to the ability of acylthioureas to form hydrogen bonds, they interact strongly with the active site. [23] Compounds bearing acylthiourea moiety are known to exhibit a wide range of pharmacological properties such as antibacterial, [24,25] antimycobacterial, [26] antifungal, [27,28] antiviral, [29] anticancer, [30] anti-inflammatory [31] and antioxidant [32] activities. In addition to these pharmacological properties of acylthiourea derivatives, it has been reported that they show antidiabetic activity by acting as α-gly and αamylase inhibitors in recent studies.…”

Section: Introductionmentioning

confidence: 99%

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

et al. 2022

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One of the most prevalent chronic metabolic disorders, diabetes mellitus, is defined by chronic hyperglycemia and the emergence of microvascular and macrovascular pathology unique to diabetes. Several diabetes problems are primarily caused by persistent hyperglycemia. In this study, aldose reductase (AR) and sorbitol dehydrogenase (SDH) enzymes were purified using chromatographic techniques from sheep kidneys and α-glycosidase purchased commercially. The inhibitory effect of seven acylthiourea compounds on the activity of these enzymes associated with diabetes was investigated. As a result of the studies, the acyl thioureas showed an inhibition effect at the micromolar level on the activity of studied enzymes. The most active compound dimethyl 1-((4-methoxybenzoyl)carbamothioyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate (2 c) had an excellent selectivity on AR with K i : 0.200 � 0.024 μM and dimethyl 1-((2,4-dichlorobenzoyl)carbamothioyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate (2 g) on SDH and αglycosidase with K i : 0.114 � 0.01 μM and K i : 055 � 0.01 μM, respectively. The findings suggest that our study will contribute to the development of innovative and/or alternative treatment strategies in the treatment of diabetes in the future since acylthiourea compounds have an effective inhibition capacity on critical enzymes associated with diabetes.

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Section: Introductionmentioning

confidence: 99%

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

et al. 2022

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“…Substantial literature supports the fact that thiourea is a potent antioxidant and has a high degree of free radical scavenging potential 38 . This antioxidant capacity of thiourea is directly linked to its anti-inflammatory and anti-cancer properties, as depicted in various studies 33 , 39 , 40 . Research has also shown that thiourea derivatives prevented the formation of melanoma skin cancer (anti-melanoma activity) 32 , 41 .…”

Section: Discussionmentioning

confidence: 93%

Probing photoprotection properties of lipophilic chain conjugated thiourea-aryl group molecules to attenuate ultraviolet-A induced cellular and DNA damages

Rana

Fatima

Yaqoob

et al. 2022

Sci Rep

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Ultraviolet-A (UVA) radiation is a major contributor to reactive oxygen species (ROS), reactive nitrite species (RNS), inflammation, and DNA damage, which causes photoaging and photocarcinogenesis. This study aimed to evaluate the UVA protective potential of lipophilic chain conjugated thiourea-substituted aryl group molecules against UVA-induced cellular damages in human dermal fibroblasts (BJ cell line). We tested a series of nineteen (19) molecules for UVA photoprotection, from which 2′,5′-dichlorophenyl-substituted molecule DD-04 showed remarkable UVA protection properties compared to the reference (benzophenone). The results indicate that DD-04 significantly reduced intracellular ROS and nitric oxide (NO) as compared to the UVA-irradiated control (p < 0.001). Moreover, the compound DD-04 showed anti-inflammatory activity as it significantly reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) pro-inflammatory cytokines produced by THP-1 (human monocytic) cells (p < 0.05). DNA damage was also prevented by DD-04 treatment in the presence of UVA. It was observed that DD-04 significantly reduced the number of cyclobutane pyrimidine dimers (CPDs) when compared to the UVA-irradiated control (p < 0.001). Finally, the DNA strand breaks were checked and a single intact DNA band was seen upon treatment with DD-04 in the presence of UVA. In conclusion, DD-04 can be considered a potential candidate UVA filter due to its photoprotective potential.

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“…Molecular docking simulations, if carried out carefully, provide detailed understanding on the ligand' mechanism of action, whether as an agonist or antagonist. In our previous studies, we obtained successful results using several in silico tools (Başoğlu et al, 2021;Efeoglu et al, 2022;Yamali et al, 2022). In our current study, induced fit docking was performed to allow amino acid residues located at the binding site to be flexible and to allow optimum fitting of the ligand to the binding pocket.…”

Section: In Silico Studiesmentioning

confidence: 99%

A new series of thiazole‐hydrazone hybrids for Akt‐targeted therapy of non‐small cell lung cancer

Orujova

Ece

Çiftçi

et al. 2022

Drug Development Research

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In an attempt to identify potent antitumor agents for the fight against non-small cell lung cancer, new thiazolyl hydrazones (2a-n) were synthesized and examined for their in vitro cytotoxic effects on A549 human lung adenocarcinoma and L929 mouse embryonic fibroblast cells by means of the MTT assay. Furthermore, the effects of the most potent anticancer agents on apoptosis and Akt inhibition were investigated. 2-[2-((Isoquinolin-5yl)methylene)hydrazinyl]−4-(4-methylsulfonylphenyl)thiazole (2k) (IC 50 = 1.43 ± 0.12 µM) and 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl]−4-(1,3-benzodioxol-5-yl)thiazole (2l) (IC 50 = 1.75 ± 0.07 µM) displayed more pronounced anticancer activity than cisplatin (IC 50 = 3.90 ± 0.10 µM) on A549 cell lines; 2-[2-((isoquinolin-5-yl)methylene)hydrazinyl] −4-(4-methoxyphenyl)thiazole (2j) (IC 50 = 3.93 ± 0.06 µM) showed anticancer activity close to cisplatin. These compounds were found to induce apoptosis in A549 cells.Compound 2j (IC 50 = 3.55 ± 0.64 µM) showed stronger Akt inhibitory activity than GSK690693 (IC 50 = 4.93 ± 0.06 µM), while compounds 2k and 2l did not cause Akt inhibition at IC 50 concentrations (1.43 and 1.75 µM, respectively). To comprehensively elucidate the binding pose of compound 2j and to provide a detailed understanding on the ligand' binding mechanism, induced-fit docking calculations were also conducted.Both in vitro and in silico studies suggest that compound 2j shows its cytotoxic and apoptotic effects on A549 cell lines via Akt inhibition. However, it is understood that compounds 2k and 2l exert their strong anticancer effects on A549 cells through different pathways.

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Novel urea-thiourea hybrids bearing 1,4-naphthoquinone moiety: Anti-inflammatory activity on mammalian macrophages by regulating intracellular PI3K pathway, and molecular docking study

Cited by 18 publications

References 66 publications

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

Investigation of The Effect of Acylthiourea Derivatives on Diabetes‐Associated Enzymes

Probing photoprotection properties of lipophilic chain conjugated thiourea-aryl group molecules to attenuate ultraviolet-A induced cellular and DNA damages

A new series of thiazole‐hydrazone hybrids for Akt‐targeted therapy of non‐small cell lung cancer

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