Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives

Kuzu, Burak; Ergüç, Ali; Karakuş, Fuat; Arzuk, Ege

doi:10.1007/s00044-023-03090-2

Cited by 3 publications

(6 citation statements)

References 30 publications

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“…The obtained thiazole hydrazone derivatives (16 a-t) were used in the next step without further purification. [26] Synthesis of compounds 17 a-t. A chilled solution of 3 mmol N, Ndimethyl formamide (DMF), and 3 mmol POCl 3 was added dropwise on each other and stirred for 15 min at 0 °C. A solution of 1 mmol thiazole hydrazone derivatives (16 a-t) in DMF (3 mL) was added dropwise to the reaction mixture and heated at 80 °C for 6 h. The reaction mixture was cooled to room temperature, transferred to 20 ml of an ice-water mixture, and stirred for 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…The crude products (17 a-t) were purified by column chromatography on silica gel eluting with n-hexane/EtOAc (5/1). [26] Synthesis of final compounds 19 a-t. To a solution of compounds 17 a-t (1 mol) in n-PrOH (5 mL) was added NH 2 OH-HCl (1.2 mol) portionwise at room temperature for 10 min. The resulting mixture was refluxed at 90 °C for 3 hours and the formation of oxime derivatives (18 a-t) was observed under TLC control.…”

Section: Methodsmentioning

confidence: 99%

“…Initially, the conversion of substituted acetophenone compounds (12 a-j) with thiosemicarbazide (13) to thiosemicarbazone (14 a-j) and their next step reactions with alpha-bromo acetophenone reagents (15 k-t) to thiazole hydrazone derivatives (16 a-t) were prepared according to our previous work. [26] The compounds (16 a-t) obtained after the mentioned step were heated under Vilsmeier-Haack conditions (POCl 3 , DMF) at 80 °C for 1 h., and then the target compounds (17 a-t) were synthesized with high yield by neutralization. Finally, the conversion of the carbaldehyde group to the oxime (18 a-t) followed by the nitrile group was carried out in a twostep reaction to obtain the target compounds 19 a-t.…”

Section: Chemistrymentioning

confidence: 99%

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Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

Arzuk,

Karakuş,

Ergüç

et al. 2024

ChemistrySelect

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In this study, a series of derivatives of pyrazole hybrid structures containing carbonitrile and substituted thiazole moiety were designed to search for selective COX‐2 inhibition. The designed target structures were synthesized with easy, practical, and efficient procedures. COX‐1/2 inhibition and cytotoxic effects of the synthesized compounds were evaluated in NIH/3T3 and MDA‐MD‐231 cell lines for inhibition concentration and selectivity index. The results showed that the compounds have an inhibitory effect with higher selectivity towards COX‐2 overall in both cell lines and moderate antiproliferative activity by targeting the breast cancer cell line MDA‐MB‐231. Among the 19 compounds synthesized (19 a–t), especially compound 19 m was found to be highly effective with COX‐2 inhibition of 5.63 μM in the NIH/3T3 cell line and 4.12 μM in the MDA‐MB‐231 cell line. Moreover, molecular docking studies showed that the compounds indeed exhibited higher affinity for the COX‐2 active site. The theoretical ADMET properties of the presented compounds were calculated, and the results showed that the compounds may have a more favorable pharmacokinetic effect profile than the selective COX‐2 inhibitor Celecoxib, thus promising COX‐2 inhibitor drug candidates for the future.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

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Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

Arzuk,

Karakuş,

Ergüç

et al. 2024

ChemistrySelect

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“…The 3-(4,5-dimethyl-2-thiazolyl)-2,5diphenyl-2H-tetrazolium bromide (MTT) assay was used to evaluate cell viability in HepG2 cells exposed to OXY in a dosedependent manner in high glucose or galactose conditions as described in previous studies with minor modifications. 17,25 In brief, HepG2 cells (10 4 cells/well) exposed to OXY (6.25, 12.5, 25, 50, 100, and 250 μM) were incubated for 24 h at 37˚C with 5% CO2. Final dimethyl sulfoxide (DMSO, solvent control) and Triton X-100 (positive control) concentrations were 1%.…”

Section: Mtt Assaymentioning

confidence: 99%

Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?

ERGÜÇ,

OKUR,

KARAKUŞ

et al. 2023

Adıyaman Üniversitesi Sağlık Bilimleri Dergisi

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Aim: This study aims to evaluate the alterations in Oxypeucedanin (OXY)-mediated anticancer activity in different media. Second aim is to predict the affinity of OXY to electron transfer chain (ETC) complexes. Materials and Methods: MTT and LDH leakage assays were performed with OXY. Molecular docking studies were also conducted to predict the affinity of OXY to ETC complexes. Results: 250 µM OXY reduced viability in glucose media. ≥50 µM OXY decreased viability in galactose media. ≥50 µM OXY increased membrane disruption in galactose media. Molecular docking studies also showed that OXY might possess the capacity to bind to the inhibition sites of Complex I and IV. Conclusion: Galactose-conditioned media exacerbated the OXY-mediated cytotoxicity. Preliminary results suggested that mitotoxicity might take part in anticancer activity. Furthermore, OXY might cause ETC dysfunctions due to selective inhibition of Complex I and IV.

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“…The cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay in high glucose or galactose conditioned media as described previous studies with minor modifications [5,24]. In brief, HepG2 cells (10 4 cells/well) were exposed to ISO (12.5, 25, 50, 100, and 250 μM) for 24 h at 37˚C with 5% CO2.…”

Section: Cell Viability Assaymentioning

confidence: 99%

İzoi̇mperatori̇n Aracilikli Anti̇kanser Akti̇vi̇te: Mi̇tokondri̇yal Di̇sfonksi̇yonun Hepg2 Hücreleri̇ndeki̇ Rolü

Ergüç

Arzuk

Albayrak

et al. 2023

Ankara Ecz. Fak. Derg.

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Objective: The first goal of the present study is to investigate the role of mitochondria due to the Crabtree effect in HepG2 cells exposed to ISO in either glucose- or galactose-conditioned media. The second aim is to predict the interactions between electron transport chain (ETC) complexes and ISO, which might be the possible reason for mitochondrial dysfunction. Material and Method: Cell viability and membrane damage for HepG2 cells exposed to ISO (12.5, 25, 50, 100, and 250 µM) were assessed by MTT and LDH leakage assays in either glucose- or galactose-conditioned media. The affinity of ISO to ETC complexes was also determined by a molecular docking study. Result and Discussion: MTT assay showed that 250 µM ISO leads to cytotoxic activity in glucose-conditioned media, while 25 µM and higher concentrations of ISO decrease cell viability in galactose-conditioned media. A membrane damage assay conducted in a glucose-conditioned media assay revealed that 250 µM ISO disrupts the cell membrane. 100 and 250 µM ISO increased membrane damage in galactose-conditioned media. According to docking simulations, binding affinities of ISO to ETC complexes are in descending order: Complex IV > Complex I > Complex III > Complex II. Inhibition of complex IV by ISO inhibits the transfer of electrons from cytochrome c to oxygen, and the proton gradient collapses. The present study proposed that ISO leads to mitochondrial dysfunction via inhibition of the ETC.

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Design, synthesis, and antiproliferative activities of novel thiazolyl-pyrazole hybrid derivatives

Cited by 3 publications

References 30 publications

Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

Novel Pyrazole Derivatives Bearing Carbonitrile and Substituted Thiazole Moiety for Selective COX‐2 Inhibition

Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?

İzoi̇mperatori̇n Aracilikli Anti̇kanser Akti̇vi̇te: Mi̇tokondri̇yal Di̇sfonksi̇yonun Hepg2 Hücreleri̇ndeki̇ Rolü

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