Novel hybrid pyrrolidinedione-thiazolidinones as potential anticancer agents: Synthesis and biological evaluation

Finiuk, Nataliya; Kryshchyshyn‐Dylevych, Anna; Holota, Serhii; Klyuchivska, Olga; Kozytskiy, Andriy V.; Karpenko, Olexandr; Manko, Nazar; Ivasechko, Iryna; Stoika, Rostyslav; Lesyk, Roman

doi:10.1016/j.ejmech.2022.114422

Cited by 19 publications

(9 citation statements)

References 65 publications

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“…The p53-deficient HCT-116 p53 (−/−) colon cancer cells were donated by a Collection of the Institute for Cancer Research at Vienna Medical University (Vienna, Austria). Cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM, Biowest, France) or RPMI-1640 medium (Biowest, France), containing 10% of fetal bovine serum (FBS, Biowest, France) according to recommendations of American Type Culture Collection (ATCC), under the incubation conditions of 5% CO 2 humidity at 37 °C [ 53 ].…”

Section: Methodsmentioning

confidence: 99%

Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

et al. 2022

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Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.

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Section: Methodsmentioning

confidence: 99%

Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

et al. 2022

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“…A spectroscopic DNA interaction study was performed as previously described [ 63 ]. salmon sperm DNA (Sigma-Aldrich, USA) was diluted in Milli-Q water at 4 °C for 24 h at 1.65 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

1,4-Naphthoquinone Motif in the Synthesis of New Thiopyrano[2,3-d]thiazoles as Potential Biologically Active Compounds

et al. 2022

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A series of 11-substituted 3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones were obtained via hetero-Diels-Alder reaction of 5-alkyl/arylallylidene/-4-thioxo-2-thiazolidinones and 1,4-naphthoquinones. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. According to U.S. NCI protocols, compounds 3.5 and 3.6 were screened for their anticancer activity; 11-Phenethyl-3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d]thiazole-2,5,10-trione (3.6) showed pronounced cytotoxic effect on leukemia (Jurkat, THP-1), epidermoid (KB3-1, KBC-1), and colon (HCT116wt, HCT116 p53-/-) cell lines. The cytotoxic action of 3.6 on p53-deficient colon carcinoma cells was two times weaker than on HCT116wt, and it may be an interesting feature of the mechanism action.

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“…The diversity-oriented approach was applied for the synthesis of ciminalum-4-thiazolidinone hybrid molecules, and a series of derivatives were reported by Buzun and Finiuk [ 24 , 25 , 26 ]. For such a hybrid type, SAR analysis revealed that the presence of carboxylic acids [ 25 ], p-hydroxyphenyl [ 24 ], or (4-hydroxyphenyl)-pyrrolidine-2,5-dione [ 26 ] substituents at position 3 of the 4-thiazolidinone ring determines the most effective anti-tumor activity, while the absence of a substituent or presence of an additional ciminalum substituent at position 3 leads to a weakening in activity. Among the synthesized and screened hybrids, derivative 11 ( Figure 6 ) was cytotoxic toward MCF-7 and MDA-MB-231 breast cancer cell lines, with IC 50 values of 5.02 µM and 15.24 µM, respectively [ 25 ].…”

Section: Approved Drug–4-thiazolidinones Hybridsmentioning

confidence: 99%

“…Finiuk et al [ 26 ] reported on ciminalum–4-thiazolidinone hybrids containing phenyl-pyrrolidine-2,5-dione moieties in the molecules. The hit-compounds 14 and 15 ( Figure 6 ), possessing micromolar cytotoxic activity towards leukemia, colon cancer, CNS, and ovarian cancer cell lines, were identified following a 60 lines NCI protocol with total MG_MID GI 50 values of 1.76 and 1.73 μM, respectively.…”

Section: Approved Drug–4-thiazolidinones Hybridsmentioning

confidence: 99%

4-Thiazolidinone-Bearing Hybrid Molecules in Anticancer Drug Design

Roszczenko

Holota

Szewczyk

et al. 2022

IJMS

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Oncological diseases have currently reached an epidemic scale, especially in industrialized countries. Such a situation has prompted complex studies in medicinal chemistry focused on the research and development of novel effective anticancer drugs. In this review, the data concerning new 4-thiazolidinone-bearing hybrid molecules with potential anticancer activity reported during the period from the years 2017–2022 are summarized. The main emphasis is on the application of molecular hybridization methodologies and strategies in the design of small molecules as anticancer agents. Based on the analyzed data, it was observed that the main directions in this field are the hybridization of scaffolds, the hybrid-pharmacophore approach, and the analogue-based drug design of 4-thiazolidinone cores with early approved drugs, natural compounds, and privileged heterocyclic scaffolds. The mentioned design approaches are effective tools/sources for the generation of hit/lead compounds with anticancer activity and will be relevant to future studies.

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Novel hybrid pyrrolidinedione-thiazolidinones as potential anticancer agents: Synthesis and biological evaluation

Cited by 19 publications

References 65 publications

Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents

1,4-Naphthoquinone Motif in the Synthesis of New Thiopyrano[2,3-d]thiazoles as Potential Biologically Active Compounds

4-Thiazolidinone-Bearing Hybrid Molecules in Anticancer Drug Design

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