Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-<i>d</i>]pyrimidine derivatives as anti-cancer agents

Shaban, Rania M.; Samir, Nermin; Nissan, Yassin M.; Abouzid, Khaled A. M.

doi:10.1039/d3ra00446e

Cited by 5 publications

(1 citation statement)

References 39 publications

(49 reference statements)

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“…Then it was washed with ice-cold water (2 × 10 mL), saturated NaHCO 3 solution (1 × 10 mL), In vitro antiproliferative activity against 60 cell line panel. [101] NCI in vitro cancer screening is a two-phase process that begins with the evaluation of all compounds against a panel of 60 NCI cell lines representing leukemia, NSCLC, CNS cancer, melanoma, prostate cancer, breast cancer, renal cancer, colon cancer, and ovarian cancer at a single concentration of 10 µM. The output of a single quantity can be reported as a mean graph (Supporting Information S1: Data).…”

Section: Synthesis Of Intermediate Compoundsmentioning

confidence: 99%

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Mansour,

AboulMagd,

Abbas

et al. 2024

Archiv der Pharmazie

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Two new series of quinazoline‐chalcone hybrids were designed, synthesized as histone deacetylase (HDAC)/epidermal growth factor receptor (EGFR) dual inhibitors, and screened in vitro against the NCI 60 human cancer cell line panel. The most potent derivative, compound 5e bearing a 3,4,5‐trimethoxyphenyl chalcone moiety, showed the most effective growth inhibition value against the panel of NCI 60 human cancer cell lines. Thus, it was selected for further investigation for NCI 5 log doses. Interestingly, this trimethoxy‐substituted analog inhibited the proliferation of Roswell Park Memorial Institute (RPMI)‐8226 cells by 96%, at 10 µM with IC50 = 9.09 ± 0.34 µM and selectivity index = 7.19 against normal blood cells. To confirm the selectivity of this compound, it was evaluated against a panel of tyrosine kinase enzymes. Mechanistically, it successfully and selectively inhibited HDAC6, HDAC8, and EGFR with IC50 = 0.41 ± 0.015, 0.61 ± 0.027, and 0.09 ± 0.004 µM, respectively. Furthermore, the selected derivative induced apoptosis via the mitochondrial apoptotic pathway by raising the Bax/Bcl‐2 ratio and activating caspases 3, 7, and 9. Also, the flow cytometry analysis of RPMI‐8226 cells showed that the trimethoxy‐substituted analog produced cell cycle arrest in the G1 and S phases at 55.82%. Finally, an in silico study was performed to explore the binding interaction of the most active compound within the zinc‐containing binding site of HDAC6 and HDAC8.

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Section: Synthesis Of Intermediate Compoundsmentioning

confidence: 99%

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Mansour,

AboulMagd,

Abbas

et al. 2024

Archiv der Pharmazie

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A review on pyrimidine‐based derivatives: Synthesis and their biological application

Islam,

Akter

et al. 2024

Journal of Heterocyclic Chem

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Pyrimidine‐based derivatives have attracted a lot of interest in heterocyclic chemistry due to its versatile structure and diverse biological activities. This study provides a comprehensive overview of synthetic strategy of different pyrimidine ring and highlights their biological importance. In this article, we start off by going through the fundamental procedures for the synthesis of pyrimidine scaffolds, including both conventional and contemporary synthetic techniques. These works cover a range of therapeutic domains, such as effects that are anticancer, antibacterial, antiviral, anti‐inflammatory, antioxidant, antimalarial, and so on. Moreover, we have summarized with a discussion of future prospects and challenges in the field of pyrimidine heterocyclic chemistry. This thorough review is a significant resource for researchers in medicinal chemistry and related fields since it offers insightful information about the synthetic methods and biological applications of pyrimidine‐based derivatives.

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Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets

Mushtaq,

Wu,

Naseer

2024

Pharmacology & Therapeutics

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Design, synthesis, and biological evaluation with molecular dynamics study of novel pyrazolo[3,4-d]pyrimidine derivatives as anti-cancer agents

Abstract: Design strategy for pyrazolo[3,4-d]pyrimidine derivatives based on tandutinib structure.

Cited by 5 publications

References 39 publications

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

Quinazoline‐chalcone hybrids as HDAC/EGFR dual inhibitors: Design, synthesis, mechanistic, and in‐silico studies of potential anticancer activity against multiple myeloma

A review on pyrimidine‐based derivatives: Synthesis and their biological application

Recent drug design strategies and identification of key heterocyclic scaffolds for promising anticancer targets

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