Synthesis of 4,6-disubstituted pyrazolo[3,4-d]pyrimidine analogues: Cyclin-dependent kinase 2 (CDK2) inhibition, molecular docking and anticancer evaluation

Cherukupalli, Srinivasulu; Chandrasekaran, Balakumar; Aleti, Rajeshwar Reddy; Sayyad, Nisar; Hampannavar, Girish A.; Merugu, Srinivas Reddy; Rachamalla, Hari Krishnareddy; Banerjee, Rajkumar; Karpoormath, Rajshekhar

doi:10.1016/j.molstruc.2018.08.104

Cited by 43 publications

(22 citation statements)

References 44 publications

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“…Previously, a series of 4,6-disubstituted pyrazolo [3, 4-d]pyrimidine analogs inhibited the activity against the enzyme CDK2/cyclin E and Abl kinases as well as had anticancer attributes against MCF-7 and K-562 cell lines. 42 with IC 50 = 19.8 μM (K-562) and 18.9 μM (MCF-7) was the most efficacious and as per reports on CHO cell line it is non-toxic to normal human cells [45].…”

Section: Pyrazolo [34-d] Pyrimidine Derivativessupporting

confidence: 58%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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Background Cancer is a global health challenge, it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer. Main text Many novel pyrimidine derivatives have been designed and developed for their anticancer activity in the last few years. The present review aims to focus on the structure activity relationship (SAR) of pyrimidine derivatives as anticancer agent from the last decade. Conclusion This review intends to assist in the development of more potent and efficacious anticancer drugs with pyrimidine scaffold. Graphical abstract

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Section: Pyrazolo [34-d] Pyrimidine Derivativessupporting

confidence: 58%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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“…Several leads were identified and, of these, 19 demonstrated the best CDK2 inhibition (IC 50 = 6.8 μM) and low-micromolar potency against two cancer cell lines. 63 cMET cMET is a member of the MET family of receptor tyrosine kinases. cMET is a transmembrane receptor expressed on the surface of cells that binds the hepatocyte growth factor (HGF) ligand.…”

Section: Cdkmentioning

confidence: 99%

“…Several leads were identified and, of these, 19 demonstrated the best CDK2 inhibition (IC 50 = 6.8 μM) and low-micromolar potency against two cancer cell lines. 63 …”

Section: Pyrazolo[34- D ]Pyrimidines In Preclinicmentioning

confidence: 99%

Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold

Baillache

Unciti‐Broceta

2020

RSC Med. Chem.

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“…In the present research, we will highlight the most important aspect of pyrazolopyrimidines, in particular, pyrazolo[3,4‐ d ]pyrimidines bioisosteres of purines. Pyrazolo[3,4‐ d ]pyrimidines are reported to have various pharmacological activities viz., antiviral, anticoccidials, antimicrobial antitumor, herbicidal, antileukemic, CNS agents, tuberculostatic, antileishmanial, anti‐inflammatory and cardiovascular activities. They are also mainly found to show variable degrees of anticancer activities against HCC, cervical carcinoma, colon carcinoma, skin carcinoma, and breast adenocarcinoma, by inhibiting different types of enzymes such as EGFR‐TK, CDK, B‐Raf kinase, Src and Abl tyrosine kinase, and glycogen synthase kinase‐3 …”

Section: Introductionmentioning

confidence: 99%

Novel Pyrazolo[3,4‐d]pyrimidine‐Containing Amide Derivatives: Synthesis, Molecular Docking, In Vitro and In Vivo Antidiabetic Activity

et al. 2019

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A new series of Pyrazolo [3,4-d]pyrimidine containing amide derivatives (8 a-l) were designed, synthesized, and evaluated for their in vitro α-amylase inhibitory activity. The IC 50 values of the target compounds ranged from 1.60 � 0.48 to 2.04 � 1.20 μM as compared to the standard acarbose 1.73 � 0.05 μM. All the Pyrazolo[3,4-d]pyrimidine amide derivatives displayed good inhibitory activities, while seven analogs (8 d, 8 f, 8 g, 8 h, 8 i, 8 j and 8 k) exhibited more or less equipotent activity with IC 50 values 1.77 � 2.84, 1.65 � 0.45, 1.66 � 2.24, 1.73 � 0.37, 1.60 � 0.48, 1.75 � 0.36 and 1.64 � 0.03 μM respectively. Further, the most potent α-amylase inhibitors 8 d and 8 k were also screened for their in vivo antidiabetic activity against alloxan induced diabetic rat model at the dose of 25 and 50 mg/kg. Oral administration of these tested compounds significantly reduced the fasting blood glucose levels in dose dependent manner. The hypoglycemic effects of these compounds were more evident at 3 h and 5 h after administration of tested compounds which was similar to the effect displayed by the positive control. In addition, the binding energies calculated from the docking studies with the α-amylase enzyme (PDB ID: 1HNY) and biological activities indicate that the compounds containing nitro moiety on the phenyl group contributed significantly towards the antidiabetic activity.[a] Dr.

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Synthesis of 4,6-disubstituted pyrazolo[3,4-d]pyrimidine analogues: Cyclin-dependent kinase 2 (CDK2) inhibition, molecular docking and anticancer evaluation

Cited by 43 publications

References 44 publications

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Recent developments in anticancer kinase inhibitors based on the pyrazolo[3,4-d]pyrimidine scaffold

Novel Pyrazolo[3,4‐d]pyrimidine‐Containing Amide Derivatives: Synthesis, Molecular Docking, In Vitro and In Vivo Antidiabetic Activity

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