Synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives and exploring molecular and cytotoxic properties based on DFT and molecular docking studies

Fouda, Ahmed M.; El-Nassag, Mohammed A. A.; Elhenawy, Ahmed A.; Shati, Ali A.; Alfaifi, Mohammad Y.; Elbehairi, Serag Eldin I.; Alam, Mohammed Mujahid; El‐Agrody, Ahmed M.

doi:10.1016/j.molstruc.2021.131555

Cited by 22 publications

(13 citation statements)

References 68 publications

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“…Very recently, 1,4-dihydropyrano[2,3- c ]pyrazole derivatives 124 were obtained in excellent yields through a piperidine-catalyzed four-component reaction of β -ketoesters 8 , malononitrile 2 , aryl/heteroaryl aldehydes 1 , and hydrazine hydrate 4 in ethanol under microwave heating at 140 °C for 2 min ( Scheme 14 ) [ 112 ]. After completion of the reaction, the product was filtered, washed with methanol, and recrystallized from ethanol.…”

Section: Multicomponent Synthesis Of Biologically Active Pyrazole Der...mentioning

confidence: 99%

“…In addition, the compounds 124a (R = Me, R 1 = 4-fluorophenyl) and 124e (R = Me, R 1 = 4-(piperidin-1-yl)phenyl) showed better cytotoxicity against SKOV-3 and A549 cell lines with IC 50 values of 2.0 and 1.1 μM, respectively. Molecular docking studies were performed for all synthesized compounds against His-tag human thymidylate synthase (HT-hTS) in a complex with 2′-deoxyuridine 5′-monophosphate (dUMP) (PDB: 6QXH) [ 112 ]. The compounds 124a (R = Me, R 1 = 4-fluorophenyl), 124b (R = C 6 H 5 , R 1 = 4-fluorophenyl), and 124f (R = C 6 H 5 , R 1 = 4-(piperidin-1-yl)phenyl) stabilized in a TS binding pocket similar to dUMP through an arrangement of the pyranopyrazole cluster in perpendicular mode with Tyr270 via a hydrogen bond interaction, while the compounds 124c (R = Me, R 1 = 4-(1 H -pyrrol-1-yl)phenyl) and 124d (R = C 6 H 5 , R 1 = 4-(1 H -pyrrol-1-yl)phenyl) occupied the binding pocket by interaction with Asn238.…”

Section: Multicomponent Synthesis Of Biologically Active Pyrazole Der...mentioning

confidence: 99%

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Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

2022

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Pyrazole and its derivatives are considered a privileged N-heterocycle with immense therapeutic potential. Over the last few decades, the pot, atom, and step economy (PASE) synthesis of pyrazole derivatives by multicomponent reactions (MCRs) has gained increasing popularity in pharmaceutical and medicinal chemistry. The present review summarizes the recent developments of multicomponent reactions for the synthesis of biologically active molecules containing the pyrazole moiety. Particularly, it covers the articles published from 2015 to date related to antibacterial, anticancer, antifungal, antioxidant, α-glucosidase and α-amylase inhibitory, anti-inflammatory, antimycobacterial, antimalarial, and miscellaneous activities of pyrazole derivatives obtained exclusively via an MCR. The reported analytical and activity data, plausible synthetic mechanisms, and molecular docking simulations are organized in concise tables, schemes, and figures to facilitate comparison and underscore the key points of this review. We hope that this review will be helpful in the quest for developing more biologically active molecules and marketed drugs containing the pyrazole moiety.

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Section: Multicomponent Synthesis Of Biologically Active Pyrazole Der...mentioning

confidence: 99%

Section: Multicomponent Synthesis Of Biologically Active Pyrazole Der...mentioning

confidence: 99%

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

2022

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“…The final pose was chosen according to the lowest Δ G and lowest RMSD, while the binding-efficiency (BE) was selected from the highest Δ G . The inhibition-constant ( K i ) was generated for 6–19 hybrids to promote validation of the BE, and should be in the range of 0.1–1.0 μM, ideally lower than 10 nM, 47 where a lower K i value indicates a higher BE efficiency for the molecules. All the calculated parameters for the compounds ( 6–19 ) and 5-FU against TS are tabulated in Table 5.…”

Section: Resultsmentioning

confidence: 99%

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

et al. 2023

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“…The other tested compounds showed lower interaction energy than the reference erlotinib. All compounds showed a normal range of bioactivity parameters Ki, LE, and FQ [ 41 ].…”

Section: Resultsmentioning

confidence: 99%

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

et al. 2022

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In the current study, new benzimidazole-based 1,3,4-oxadiazole derivatives have been synthesized and characterized by NMR, IR, MS, and elemental analysis. The final compounds were screened for cytotoxicity against MDA-MB-231, SKOV3, and A549 cell lines and EGFR for inhibitory activities. Compounds 10 and 13 were found to be the most active against all the tested cell lines, comparable to doxorubicin, and exhibited significant inhibition on EGFR kinase, with IC50 0.33 and 0.38 μM, respectively, comparable to erlotinib (IC50 0.39 μM). Furthermore, these two compounds effectively suppressed cell cycle progression and induced cell apoptosis in MDA-MB-231, SKOV3, and A549 cell lines. The docking studies revealed that these compounds showed interactions similar to erlotinib at the EGFR site. It can be concluded that the synthesized molecules effectively inhibit EGFR, can arrest the cell cycle, and may trigger apoptosis and therefore, could be used as lead molecules in the development of new anticancer agents targeting EGFR kinase.

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Synthesis of 1,4-dihydropyrano[2,3-c]pyrazole derivatives and exploring molecular and cytotoxic properties based on DFT and molecular docking studies

Cited by 22 publications

References 68 publications

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

Recent Applications of the Multicomponent Synthesis for Bioactive Pyrazole Derivatives

Design, synthesis and biological evaluation of new eugenol derivatives containing 1,3,4-oxadiazole as novel inhibitors of thymidylate synthase

Cell Cycle Arrest and Apoptosis-Inducing Ability of Benzimidazole Derivatives: Design, Synthesis, Docking, and Biological Evaluation

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