Synthesis and Anticancer Activity of New Pyridine-Thiophene and
Pyridine-Furan Hybrid Compounds, Their Sugar Hydrazone, and Glycosyl
Derivatives

Khalaf, Hemat S.; Tolan, Hala E. M.; El‐Bayaa, M. N.; Radwan, Mohamed A. A.; El-Manawaty, May A.; El‐Sayed, Wael A.

doi:10.1134/s1070363220090182

Cited by 15 publications

(15 citation statements)

References 29 publications

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“…Saccharides have the characteristics of low toxicity, high polarity, and high solubility. In the area of medicinal chemistry, glycol derivatives and glycosyl modification compounds have shown a wide range of pharmacological activities [ 18 , 19 , 20 , 21 , 22 ]. In the research on CA IX inhibitors, saccharide-modified compounds have achieved remarkable success, and various molecules of saccharide-modified CA IX inhibitors have been reported [ 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

Zhang

Zhong

Han

et al. 2021

IJMS

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A series of saccharide-modified thiadiazole sulfonamide derivatives has been designed and synthesized by the “tail approach” and evaluated for inhibitory activity against carbonic anhydrases II, IX, and XII. Most of the compounds showed high topological polar surface area (TPSA) values and excellent enzyme inhibitory activity. The impacts of some compounds on the viability of HT-29, MDA-MB-231, and MG-63 human cancer cell lines were examined under both normoxic and hypoxic conditions, and they showed certain inhibitory effects on cell viability. Moreover, it was found that the series of compounds had the ability to raise the pH of the tumor cell microenvironment. All the results proved that saccharide-modified thiadiazole sulfonamides have important research prospects for the development of CA IX inhibitors.

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Section: Introductionmentioning

confidence: 99%

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

Zhang

Zhong

Han

et al. 2021

IJMS

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“…The IR spectra were documented on a perkin-Elmer 1720 FTIR spectrometer (cm -1 ), using KBr disks. 1 H NMR and 13 C NMR spectra were determined on a varian Gemini spectrometer (300 MHz) using DMSO-d6 or CDCl3 as a solvent and TMS (δ) as the internal standard. Mass spectra were obtained using Mass spectra were obtained using a CC 2010 Shimadzu Gas chromatography instrument mass spectrometer (70 eV).…”

Section: Chemistrymentioning

confidence: 99%

“…IR (KBr) cm −1 , ν: 3428-3298 (NH2), 3159 (NH), 1638(C=O). 1 General procedures for the preparation of triazenes 5a-5c. A mix of the pyrazolpyridine 1 (1.5 g, 9.35 mmol), conc.…”

Section: General Procedures For the Preparation Of 2a-2cmentioning

confidence: 99%

“…We need to improve novel chemotherapeutic agents which are more active as antitumor and taking into consideration decrease side effects which represent a great attention and actual challenge to medicinal chemists to develop a safe and no-side effected anticancer drug. In such direction, an interesting strategy involving the synthesis of novel hybrid molecules incorporating varied well-known active cores, was found efficient in designing and discovering potent anticancer leads [1,2].…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Cytotoxic Activity of New Substituted Pyrazolo[3,4-b]pyridine Derivatives and Their Acyclic Nucleoside Analogs

et al. 2021

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As an important strategy, including incorporation of more than active core in one molecule, for finding potent candidates against cancer cells, a number of functionalized pyrazolopyridin derivatives linked to oxadiazole, dioxolane, acyclic sugar and fluorene ring systems, were synthesized through heterocyclization reactions. The derived sugar hydrazone and the corresponding acyclic C-nucleoside analog in addition to acyclic N-nucleoside were also prepared. The behavior of the afforded compounds as possible cytotoxic agents against human HTC116 and MCF7 cancer cells was investigated and the results showed that compounds 11-13 showed the highest activities against the two cancer cells. Other compounds revealed a type of selectivity toward one cancer cell while the activity was relatively lost against the other cancer cell line.

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“…The incorporation of more than one heterocyclic core in one hybrid structure, known as molecular hybridization, gained considerable interest in the design and synthesis of bioactive compounds [ 10 , 11 , 12 ]. The pyridine core is found in a variety of biologically active compounds possessing a broad spectrum of bioactivities [ 13 , 14 ]. The pyrazolo[3,4-b]pyridine framework is a promising heterocyclic scaffold that has gained renewed interest displaying a broad spectrum of biological activities such as antitumor inhibiting CDK2 [ 15 , 16 , 17 , 18 , 19 ] and glycogen synthase kinase-3 (GSK-3) inhibitors [ 20 ].…”

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 Pyridine-Thiophene and Pyridine-Furan Hybrid Compounds, Their Sugar Hydrazone, and Glycosyl Derivatives

Cited by 15 publications

References 29 publications

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

Synthesis, Molecular Docking Analysis and Biological Evaluations of Saccharide-Modified Thiadiazole Sulfonamide Derivatives

Synthesis and Cytotoxic Activity of New Substituted Pyrazolo[3,4-b]pyridine Derivatives and Their Acyclic Nucleoside Analogs

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

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