Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Vekariya, Mayur K.; Vekariya, Rajesh H.; Brahmkshatriya, Pathik S.; Shah, Nisha K.

doi:10.1111/cbdd.13334

Cited by 15 publications

(2 citation statements)

References 25 publications

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“…Cyclin-dependent kinases (CDKs) are one class of serine/threonine proteins. These serine/threonine proteins are renowned for their important functions in the regulation of cell divisions [23]. Cancer and other disorders associated with aberrant cellular production can be effectively treated by blocking several enzymes that regulate the cell cycle's progression [24].…”

Section: Discussionmentioning

confidence: 99%

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

Ahmad¹,

Ansari

Alsayari

et al. 2022

Pharmaceuticals

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Anthraquinones (AQs) are present in foods, dietary supplements, pharmaceuticals, and traditional treatments and have a wide spectrum of pharmacological activities. In the search for anti-cancer drugs, AQ derivatives are an important class. In this study, anthraquinone aglycons chrysophanol (Chr), emodin (EM) and FDA-approved anticancer drug fluorouracil were analyzed by molecular docking studies against receptor molecules caspase-3, apoptosis regulator Bcl-2, TRAF2 and NCK-interacting protein kinase (TNIK) and cyclin-dependent protein kinase 2 (CDK2) as novel candidates for future anticancer therapeutic development. The ADMET SAR database was used to predict the toxicity profile and pharmacokinetics of the Chr and EM. Furthermore, in silico results were validated by the in vitro anticancer activity against HCT-116 and HeLa cell lines to determine the anticancer effect. According to the docking studies simulated by the docking program AutoDock Vina 4.0, Chr and EM had good binding energies against the target proteins. It has been observed that Chr and EM show stronger molecular interaction than that of the FDA-approved anticancer drug fluorouracil. In the in vitro results, Chr and EM demonstrated promising anticancer activity in HCT-116 and HeLa cells. These findings lay the groundwork for the potential use of Chr and EM in the treatment of human colorectal and cervical carcinomas.

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Section: Discussionmentioning

confidence: 99%

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

Ahmad¹,

Ansari

Alsayari

et al. 2022

Pharmaceuticals

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“…Therefore, there is a need to develop new anti-cancer agents [ 2 , 3 ]. Literature survey indicated that pyrimidine analogs are of considerable interest in drug discovery [ 4 , 5 , 6 , 7 , 8 ]. They possess remarkable biological activity especially as anti-cancer and anti-viral agents due to their resemblance to cellular pyrimidine bases involved in nucleic acids formation.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

Fatahala

Sayed

Mahgoub

et al. 2021

IJMS

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In an effort to discover potent anticancer agents, 2-thiouracil-5-sulfonamides derivatives were designed and synthesized. The cytotoxic activity of all synthesized compounds was investigated against four human cancer cell lines viz A-2780 (ovarian), HT-29 (colon), MCF-7 (breast), and HepG2 (liver). Compounds 6b,d–g, and 7b showed promising anticancer activity and significant inhibition of CDK2A. Moreover, they were all safe when tested on WI38 normal cells with high selectivity index for cancer cells. Flow cytometric analysis for the most active compound 6e displayed induction of cell growth arrest at G1/S phase (A-2780 cells), S phase (HT-29 and MCF-7 cells), and G2/M phase (HepG2 cells) and stimulated the apoptotic death of all cancer cells. Moreover, 6e was able to cause cycle arrest indirectly through enhanced expression of cell cycle inhibitors p21 and p27. Finally, molecular docking of compound 6e endorsed its proper binding to CDK2A, which clarifies its potent anticancer activity.

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Synthesis, in vitro anticancer activity and in silico studies of certain pyrazole-based derivatives as potential inhibitors of cyclin dependent kinases (CDKs)

Mohammed

Mahmoud

George

et al. 2021

Bioorganic Chemistry

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Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation

Cited by 15 publications

References 25 publications

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

In Vitro, Molecular Docking and In Silico ADME/Tox Studies of Emodin and Chrysophanol against Human Colorectal and Cervical Carcinoma

Synthesis of Novel 2-Thiouracil-5-Sulfonamide Derivatives as Potent Inducers of Cell Cycle Arrest and CDK2A Inhibition Supported by Molecular Docking

Synthesis, in vitro anticancer activity and in silico studies of certain pyrazole-based derivatives as potential inhibitors of cyclin dependent kinases (CDKs)

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