Antiproliferative Activity of Some Newly Synthesized Substituted Nicotinamides Candidates Using Pyridine-2(1<i>H</i>) thione Derivatives as Synthon

Elnaggar, Dina H.; Mohamed, Ashraf M.; Hafez, Naglaa A. Abdel; Azab, M. M.; Elasasy, M. E. A.; Awad, Hanem M.; Farghaly, Thoraya A.; Amr, Abd El‐Galil E.

doi:10.1021/acsomega.1c06951

Cited by 15 publications

(2 citation statements)

References 36 publications

(54 reference statements)

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“…Thieno[2,3- b ]pyridine derivatives occupy a unique position and have received considerable attention due to their diverse pharmacological activities, which include anticancer, , antiviral, , anti-inflammatory, , antimicrobial, , antidiabetic, , and osteogenic antiproliferative activity. Furthermore, they can be used as adenosine A1 receptor ligands for the potential treatment of epilepsy and as antiplatelet drugs .…”

Section: Introductionmentioning

confidence: 99%

Utility of 2-Chloro-N-arylacetamide and 1,1′-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines]

Salem,

Abdullah,

Zaki

et al. 2024

ACS Omega

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A series of novel thieno [2,3-b]pyridines linked to N-aryl carboxamides or (carbonylphenoxy)-N-(aryl)acetamides, as well as bis(thieno[2,3-b]pyridines) linked to piperazine core via methanone or carbonylphenoxyethanone units, were synthesized by treating the appropriate chloroacetyl-or bis-bromoacetyl derivatives with 2mercaptonicotinonitrile derivatives in ethanolic sodium ethoxide at reflux. The spectral data were used to determine the compositions of novel compounds.

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Section: Introductionmentioning

confidence: 99%

Utility of 2-Chloro-N-arylacetamide and 1,1′-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines]

Salem,

Abdullah,

Zaki

et al. 2024

ACS Omega

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“…Based on these findings, and as a continuation of our earlier efforts in the production of bioactive heterocyclic compounds (Alhasani et al, 2022;Almehmadi et al, 2021;Alsaedi, Almehmadi, et al, 2022;Alsaedi, Farghaly, et al, 2022;Althagafi et al, 2019;Elnaggar et al, 2022;Farghaly et al, 2022;Janssen & Jageneau, 1957;Katowah et al, 2022;Mahmouda et al, 2021;Shaaban et al, 2022), we have synthesized new series of tricyclic/tetracyclic benzosuberane carrying morpholine moiety with the aim of designing effective antibreast cancer agents that can inhibit the CDK2 enzyme. Here, the crucial binding interactions with the ATP binding site of CDK2 were preserved (Figure 3) by retaining the planar benzosuberane scaffold that is linked to groups capable of binding to the hinge region key residues via hydrogen bonds and linked to phenyl group that was expected to occupy the hydrophobic pocket of the enzyme.…”

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confidence: 99%

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors

Farghaly

Abbas

Al‐Sheikh

et al. 2023

Drug Development Research

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With the aim of developing cyclin‐dependent kinase 2 (CDK2) inhibitors with strong antibreast cancer efficacy, new tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives were synthesized. The newly synthesized tri‐ and tetracyclic derivatives were achieved from the reaction of 4‐(4‐morpholin‐4‐yl‐phenyl)−1,3,4,5,6,7‐hexahydro‐benzo[6,7]cyclohepta[1,2‐d]pyrimidine‐2‐thione (5) with α‐haloketone derivatives as hydrazonyl chlorides, phenacyl bromide derivatives, chloroacetone, and ethyl substituted acetate derivatives. The MCF‐7 and MDA‐MB‐231 breast cancer cell lines were utilized to examine the anticancer properties. Compounds 5 and 8 were shown to be the most effective, with half‐maximal inhibitory concentration (IC50) values between 5.73 and 9.11 µM, which are on the level with doxorubicin. Mechanistic studies showed that 5 and 8 caused tumor cell death by inducing apoptosis and they also produced cancer arrest in the S phase of the cell cycle. In addition, compounds 5 and 8 showed strong anti‐CDK2 action (IC50 = 0.112 and 0.18 µM, respectively) comparable to roscovitine (IC50 = 0.127 µM). Moreover, the docking result demonstrated that derivatives 5 and 8 fit into the CDK2 active site in the proper orientation.

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One pot multi-component synthesis of novel functionalized pyrazolo furan-2(5H)-one derivatives: in vitro, DFT, molecular docking, and pharmacophore studies, as coronavirus inhibitors

Elsisi,

Mohamed,

Seadawy

et al. 2024

Mol Divers

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New and facile one-pot approach for the syntheses of 12 derivatives of 3,5-disubstituted furane-2(5H)-one (4a–l) from easily available starting materials. The suitable synthetic procedures for selective synthesis of diverse furane-2(5H)-one derivatives were achieved via multi-component condensation of 1,3-diphenyl-1H-pyrazole-4-carbaldehyde (1), pyruvic acid and different aromatic amines 3a–l in good to high yields and short reaction time by refluxing in acetic acid as well as obtained by another method (method B) when unsaturated arylidene pyruvic acid 6 was refluxed with different aromatic amines in acetic acid but in smaller yield than method A. Structures of the prepared compounds were elucidated by elemental analysis and spectral data as mass, IR, 1H-NMR and 13C-NMR spectroscopy. The antiviral efficacy of compounds 4a–l against SARS-CoV-2 was evaluated using the MTT assay. It was demonstrated that synthetic compounds 4c–e and 4h–j have a potent and selective inhibitory effect on SARS-CoV-2, a strain obtained from Egyptian patients. We utilized density-functional theory (DFT) analyses to deduce the molecular structures and topologies of the more energetic molecules. Molecular docking studies were performed against the SARS-CoV-2 main protease (PDB ID: 6Y84) and the SARS-CoV-2 Nsp9 RNA binding protein (PDB ID: 6W4B) to study the binding mechanism, non-bonding interactions, and binding affinity. Lastly, a hypothetical pharmacophore model was constructed by applying the Molecular Operating Environment (MOE) tool and eleven pharmaceuticals with proven antiviral activity.

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Antiproliferative Activity of Some Newly Synthesized Substituted Nicotinamides Candidates Using Pyridine-2(1H) thione Derivatives as Synthon

Cited by 15 publications

References 36 publications

Utility of 2-Chloro-N-arylacetamide and 1,1′-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines]

Utility of 2-Chloro-N-arylacetamide and 1,1′-(Piperazine-1,4-diyl)bis(2-chloroethanone) as Versatile Precursors for Novel Mono- and Bis[thienopyridines]

Synthesis of tricyclic and tetracyclic benzo[6,7]cycloheptane derivatives linked morpholine moiety as CDK2 inhibitors

One pot multi-component synthesis of novel functionalized pyrazolo furan-2(5H)-one derivatives: in vitro, DFT, molecular docking, and pharmacophore studies, as coronavirus inhibitors

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