Novel 6,7,8-trihydrobenzo[6',7']cyclohepta[2',1'-e]pyrazolo[2,3-a]pyrimidine derivatives as Topo IIα inhibitors with potential cytotoxic activity

Farghaly, Thoraya A.; Abdulwahab, Hanan Gaber; Medrasi, Hanadi Y.; Al‐Sheikh, Mariam A.; Katowah, Dina F.; Alsaedi, Amani M. R.

doi:10.1016/j.bioorg.2022.106043

Cited by 14 publications

(3 citation statements)

References 24 publications

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“…In addition, pyrazolo [1,5a]pyrimidines have a wide spectrum of biological activity in different fields and are widely used as cyclin-dependent kinase (CDK) inhibitors, which transduce mitogenic signals and improve cell proliferation, migration, differentiation, metabolism and immune responses. [38][39][40][41][42][43][44][45][46][47][48][49] Some pyrazolo [1,5-a]pyrimidine structures are considered as approved drugs such as zaleplon, indiplon, and lorediplon, have been approved as sedativehypnotics and for treatment of insomnia. In addition, ocinaplone is used as anxiolytic drug, and anagliptin as a treatment for type 2 diabetes mellitus (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…Pyrazolo[1,5‐ a ]pyrimidines are fused heterocyclic ring systems known as bioisosteres of the adenine ring, and are required for all aspects of cellular life. In addition, pyrazolo[1,5‐a]pyrimidines have a wide spectrum of biological activity in different fields and are widely used as cyclin‐dependent kinase (CDK) inhibitors, which transduce mitogenic signals and improve cell proliferation, migration, differentiation, metabolism and immune responses [38–49] . Some pyrazolo[1,5‐ a ]pyrimidine structures are considered as approved drugs such as zaleplon, indiplon, and lorediplon, have been approved as sedative‐hypnotics and for treatment of insomnia.…”

Section: Introductionmentioning

confidence: 99%

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Novel Class of Fluorinated Pyrazolo[1,5‐a]pyrimidines as CDK5 and Bcl2 Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Studies

Said Mohamed,

Atwa Saad,

Hanafy Metwally

2023

ChemistrySelect

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New pyrazolo[1,5‐a]pyrimidines were designed and synthesized based on the structural analysis of known CDK5 inhibitors. Biological evaluations showed that the IC50 of the most potent compounds 3 c and 5 b targeting normal WI38 (human lung cells) were 74.13±4.0 and 56.19±3.5 μM, respectively and showed safety profile in normal cells compared to doxorubicin with IC50 of 6.27±0.5 μM. Compounds 3 c and 5 b, demonstrated potent CDK5 inhibitory activity with IC50=0.36±0.02 and 0.226±0.01 μM, respectively compared to roscovitine of IC50 value 0.149±0.007 μM. Compound 5 b also cause a significantly increased the percentage of cells at phases in S by 1.2 fold, compared to untreated cells. It was found that downregulation of Bcl2 expression by 3 and 6 folds for 3 c and 5 b, respectively than that the control in breast cell. In addition, examination of the induction of apoptosis by 5 b demonstrated that compound 5 b significantly increased the early and late apoptotic ratio by about 65 and 66 folds, respectively, proving that compound 5 b significantly induces apoptotic by 34.5 %. Moreover, the pharmacokinetic properties of 3 c and 5 b were predicted using ADME calculations, which revealed that they inhibit some CYP450 enzymes in the liver.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Novel Class of Fluorinated Pyrazolo[1,5‐a]pyrimidines as CDK5 and Bcl2 Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Studies

Said Mohamed,

Atwa Saad,

Hanafy Metwally

2023

ChemistrySelect

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“…In the light of these facts and in continuation of our effort toward the discovery of potent anticancer agents, 24–36 herein, novel thiazole derivatives were designed and synthesized as potent B-RAFV600E kinase inhibitors with potential anticancer activities, based on the clinically-approved B-RAFV600E inhibitor, dabrafenib. The design of our target compounds is illustrated in Fig.…”

Section: Introductionmentioning

confidence: 99%

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma

et al. 2022

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Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

2024

Archiv der Pharmazie

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Breast cancer stands as the leading cause of cancer‐related deaths among women globally, but current therapy is restricted to the serious adverse effects and multidrug resistance, necessitating the exploration of novel, safe, and efficient anti‐breast cancer chemotherapeutic agents. Pyrazoles exhibit excellent potential for utilization as effective anti‐breast cancer agents due to their ability to act on various biological targets. Particularly, pyrazole hybrids demonstrated the advantage of targeting multiple pathways, and some of them, which are exemplified by larotrectinib (pyrazolo[1,5‐a]pyrimidine hybrid), can be applied for breast cancer therapy. Thus, pyrazole hybrids hold great promise as useful therapeutic interventions for breast cancer. The aim of this review is to summarize the current scenario of pyrazole hybrids with in vitro and/or in vivo anti‐breast cancer potential, along with the modes of action and structure–activity relationships, covering articles published from 2020 to the present, to streamline the development of rational, effective and safe anti‐breast cancer candidates.

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Novel 6,7,8-trihydrobenzo[6',7']cyclohepta[2',1'-e]pyrazolo[2,3-a]pyrimidine derivatives as Topo IIα inhibitors with potential cytotoxic activity

Cited by 14 publications

References 24 publications

Novel Class of Fluorinated Pyrazolo[1,5‐a]pyrimidines as CDK5 and Bcl2 Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Studies

Novel Class of Fluorinated Pyrazolo[1,5‐a]pyrimidines as CDK5 and Bcl2 Inhibitors: Design, Synthesis, Biological Evaluation, Molecular Docking and ADME Studies

Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma

Current scenario of pyrazole hybrids with anti‐breast cancer therapeutic applications

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