Synthesis and Anticancer Activity of New ((Furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole Acyclic Sugar Derivatives

Kassem, Asmaa F.; Nassar, Ibrahim F.; Abdel‐Aal, Mohammed T.; Awad, Hanem M.; El‐Sayed, Wael A.

doi:10.1248/cpb.c19-00280

Cited by 56 publications

(25 citation statements)

References 37 publications

(46 reference statements)

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“…The antiproliferative activity of the test compounds against HepG2, and MCF-7 human cancer-cell lines were evaluated by MTT assay. The detailed methodology procedure was reported [ 27 , 28 , 29 ].…”

Section: Methodsmentioning

confidence: 99%

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

et al. 2020

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A series of 3-ethyl(methyl)-2-thioxo-2,3-dihydrobenzo[g]quinazolines (1–17) were synthesized, characterized, and evaluated in vitro for their antiangiogenesis VEGFR-2-targeting, antiproliferative, and antiapoptotic activities against breast MCF-7 and liver HepG2 cells. Flow cytometry was used to determine cancer-cell cycle distributions, and apoptosis was detected using annexin-V-FITC (V) and propidium iodide (PI) dyes. Fluorescence microscopy, in combination with Hoechst staining was used to detect DNA fragmentation. Most of the tested benzo[g]quinazolines demonstrated promising activity (IC50 = 8.8 ± 0.5–10.9 ± 0.9 μM) and (IC50 = 26.0 ± 2.5–40.4 ± 4.1 μM) against MCF-7 and HepG2, respectively. Doxorubicin was used as a reference drug. Compounds 13–15 showed the highest activity against both cancer cell lines. Differential effects were detected by cell-cycle analysis, indicating similarities in the actions of 13 and 14 against both MCF7 and HepG2, involving the targeting of G1 and S phases, respectively. Compound 15 showed similar indices against both cells, indicating that its cytotoxicity toward the examined cancer cells could be unselective. Interestingly, 14 and 15 showed the highest apoptosis (30.76% and 25.30%, respectively) against MCF-7. The DNA fragmentation results agreed well with the apoptosis detected by flow cytometry. In terms of antiangiogenesis activity, as derived from VEGFR-2 inhibition, 13 and 15 were comparable to sorafenib and effected 1.5- and 1.4-fold inhibition relative to the standard sorafenib. A docking study was conducted to investigate the interaction between the synthesized benzo[g]quinazolines and the ATP-binding site within the catalytic domain of VEGFR-2.

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Section: Methodsmentioning

confidence: 99%

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

et al. 2020

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“…The antiproliferative activities on the HepG-2, and MCF-7 human cancer cell lines were estimated, using the 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2Htetrazolium bromide (MTT) assay, which was grounded on the reduction of the tetrazolium salt by the mitochondrial dehydrogenases in viable cells [52,53]. The cells were dispensed in a 96 well sterile microplate (3 x 10 4 cells/well), followed by their incubation at 37 o C with a series of different concentrations of 10 µl of each compound or Doxorubicin® (positive control, in DMSO) for 48 h in a serum free medium prior to the MTT assay.…”

Section: Mtt Antiproliferative Assaymentioning

confidence: 99%

Synthesis and Antiproliferative Activity of Chalcone-Imide Derivatives Based on 3,4-Dichloro-1H-Pyrrole-2,5-dione

et al. 2020

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A series of chalcone imide derivatives,4'-aminochalcones-based dichloromaleimides,was synthesized from the reaction of 1-(4-acetylphenyl)-3,4-dichloro-1H-pyrrole-2,5-dione with various substituted aldehydes, or by treating 4'aminochalcone with 3,4-dichlorofuran-2,5-dione in an alternative path. The structures of chalcone imide derivatives were established using IR, 1 H NMR, 13 C NMR, and mass spectroscopy. Antiproliferative effects of the newly synthesized compounds have been screened on two human cancer types via the MTT assay. Compounds with p-tolyl-1H-pyrrole-2,5-dione, and 4bromophenyl-1H-pyrrole-2,5-dione derivatives, are highly active on the human liver cancer (HepG-2).On the other hand, all compounds were found to be more effective against breast cancer cells (MCF-7)than the positive control doxorubicin. The results of this work provide a basis for further research of selected chalcone-imide moiety as antiproliferative agents.

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“…On the other hand, glycoside and their analogs have been revealed as an important bioactive group of compounds with anticancer, antiviral, and antimicrobial activity. The therapeutic importance of this scaffold motivated us to develop selective procedures for the synthesis of new derivatives of pyridine incorporating pyrazolyl, imidazolyl, thienyl, and glycosyl moieties in which substituents could be arranged in a pharmacophoric pattern to display high order of anticancer activity [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 ].…”

Section: Introductionmentioning

confidence: 99%

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

et al. 2021

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New pyridine, pyrazoloyridine, and furopyridine derivatives substituted with naphthyl and thienyl moieties were designed and synthesized starting from 6-(naphthalen-2-yl)-2-oxo-4-(thiophen-2-yl)-1,2-dihydropyridine-3-carbonitrile (1). The chloro, methoxy, cholroacetoxy, imidazolyl, azide, and arylamino derivatives were prepared to obtain the pyridine-−C2 functionalized derivatives. The derived pyrazolpyridine-N-glycosides were synthesized via heterocyclization of the C2-thioxopyridine derivative followed by glycosylation using glucose and galactose. The furopyridine derivative 14 and the tricyclic pyrido[3′,2′:4,5]furo[3,2-d]pyrimidine 15 were prepared via heterocyclization of the ester derivative followed by a reaction with formamide. The newly synthesized compounds were evaluated for their ability to in vitro inhibit the CDK2 enzyme. In addition, the cytotoxicity of the compounds was tested against four different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549). The CDK2/cyclin A2 enzyme inhibitory results revealed that pyridone 1, 2-chloro-6-(naphthalen-2-yl)-4-(thiophen-2-yl)nicotinonitrile (4), 6-(naphthalen-2-yl)-4-(thiophen-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine (8), S-(3-cyano-6-(naphthaen-2-yl)-4-(thiophen-2-yl)pyridin-2-yl) 2-chloroethanethioate (11), and ethyl 3-amino-6-(naphthalen-2-yl)-4-(thiophen-2-yl)furo[2,3-b]pyridine-2-carboxylate (14) are among the most active inhibitors with IC50 values of 0.57, 0.24, 0.65, 0.50, and 0.93 µM, respectively, compared to roscovitine (IC50 0.394 μM). Most compounds showed significant inhibition on different human cancer cell lines (HCT-116, MCF-7, HepG2, and A549) with IC50 ranges of 31.3–49.0, 19.3–55.5, 22.7–44.8, and 36.8–70.7 μM, respectively compared to doxorubicin (IC50 40.0, 64.8, 24.7 and 58.1 µM, respectively). Furthermore, a molecular docking study suggests that most of the target compounds have a similar binding mode as a reference compound in the active site of the CDK2 enzyme. The structural requirements controlling the CDK2 inhibitory activity were determined through the generation of a statistically significant 2D-QSAR model.

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Synthesis and Anticancer Activity of New ((Furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole Acyclic Sugar Derivatives

Cited by 56 publications

References 37 publications

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

Synthesis and Antiproliferative Activity of Chalcone-Imide Derivatives Based on 3,4-Dichloro-1H-Pyrrole-2,5-dione

Discovery of New Pyrazolopyridine, Furopyridine, and Pyridine Derivatives as CDK2 Inhibitors: Design, Synthesis, Docking Studies, and Anti-Proliferative Activity

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