Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells

Malki, Ahmed; Ashour, Hayam M. A.; Elbayaa, Rasha Y.; Issa, Doaa A. E.; Aziz, Hassan A.; Chen, Xiaozhuo

doi:10.3109/14756366.2015.1118686

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…[8,9] In particular, pyrimidine-fused heterocyclic compounds have attracted considerable attention for their promising anticancer activity against a range of cancers, including leukaemia, colon, lung, and breast cancer, through various mechanisms. [10][11][12][13][14][15][16][17][18][19] Within the field of fused heterocyclic compounds, chromenopyrimidines have emerged as a remarkable type of molecules. Numerous studies reported in the literature have identified chromenopyrimidines (I-VII) with a promising profile as potential anticancer agents [20][21][22][23][24][25][26] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, pyrimidine derivatives have emerged as a fascinating class of compounds in medicinal chemistry due to their diverse biological and pharmacological properties [8,9] . In particular, pyrimidine‐fused heterocyclic compounds have attracted considerable attention for their promising anticancer activity against a range of cancers, including leukaemia, colon, lung, and breast cancer, through various mechanisms [10–19] …”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

Choura,

El Ghali,

Bernard

et al. 2024

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Herein we report the synthesis of ten newly substituted 3‐phenyl‐5‐aryl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidin‐4,6,11‐triones (“benzochromenopyrimidines”) in a one‐step reaction, by reacting ethyl 2‐amino‐4‐aryl‐5,10‐dioxo‐5,10‐dihydro‐4H‐benzo[g]chromene‐3‐carboxylates with aniline, and triethyl orthoformate, under acidic catalyst and solvent‐free conditions. These benzochromenopyrimidines were submitted to biological evaluation for in vitro anti‐cancer activity, several derivatives showing higher activity than commonly used chemotherapeutic agents such as oxaliplatin, 5‐fluorouracil, and paclitaxel. In particular, the 5‐(2‐Methoxyphenyl)‐3‐phenyl‐3,5‐dihydro‐4H‐benzo[6,7]chromeno[2,3‐d]pyrimidine‐4,6,11‐trione was identified as the most potent inhibitor among all the new ligands, showing significant cytotoxic activity against all the cancer cell lines tested [human colon cancer cell lines, LoVo and HCT‐116; human lung cancer cells (A549 line)], as evidenced by the significant decrease in IC50 values, while maintaining low cytotoxicity against normal cells. These promising results suggest that this compound deserves further investigation as a potential hit compound for the development of a selective anticancer drug in cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

Choura,

El Ghali,

Bernard

et al. 2024

ChemistrySelect

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A new microwave-assisted, three-component reaction of 5-aminopyrazole-4-carboxylates: Selective synthesis of substituted 5-aza-9-deaza-adenines

et al. 2018

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R 1 R 1 Yields up to 95% 24 examples 0.24 to 2.3 g scale AbstractA series of 5-aza-9-deaza-analogues of purine was effectively prepared using highly selective annulation of 1,3,5-triazine ring onto 5-aminopyrazole-4-carboxylates via a one-pot, multicomponent, microwave-assisted approach. The products were obtained in good yields and high purity. This catalyst-free method was demonstrated to be scalable and highly reproducible in different microwave reactors. Some structural features of the prepared compounds were studied in details using dynamic NMR spectroscopy and X-ray crystallography. Highlights-A practical synthesis of adenine analogues -A new scalable and reproducible microwave-assisted synthesis -Hindered rotation study by dynamic NMR spectroscopy Keywords Pyrazole Purine isostere Multicomponent reaction Pyrazolo[1,5-a][1,3,5]triazine Dynamic NMR spectroscopy

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Design and Synthesis of Novel Thioethers Derived from 1,5-Diphenyl-6- thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones as Antiangiogenic Agents

Malki

Issa

Elbayaa

et al. 2018

LDDD

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Background: In attempts to discover new antiangiogenic entities, a novel series of thioethers derived from 6-thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidine-4(5H)ones was considered and designed. Methods: Virtual screening was carried out through docking of the compounds into the vascular endothelial growth factor and matrix metalloproteinase-9 binding sites. Molecular docking studies were performed using Lamarckian Genetic Algorithm. Compounds possessing lowest ligandprotein pairwise interaction energies were synthesized and screened for their antiproliferative activities against five cancer cell lines namely MHCC97H (liver), MDA-MB 231 (Breast), Colo205 (Colon), A549 (lung), A498 (kidney) and IC50 values were determined for the most potent compounds. Additionally, they were tested for their antiangiogenic activities by testing their ability to inhibit Human Umbilical Vein Endothelial Cell (HUVEC), cord formation and migration in response to chemoattractant. Results: Three compounds 2a, 2b and 5b showed significant antiangiogenic activities. The allyl thioether 2b was the most active with chemotaxis activity data nearly comparable to that of the positive control, TNP-470. Additionally, 2a, 2b and 5b, contrary to TNP-470, interfered with the migration of HUVECs in response to vascular endothelial growth factor rather than endothelial cells proliferation or cord formation. Compounds 2a, 2b and 5b were also investigated for their inhibitory effects on MMPs to investigate the relationship between their angiogenic activity and MMPs. Results revealed that compound 2b was the most effective MMP-9 inhibitor in this series. Additionally, compound 2b reduced the expression levels of VEGF and pERK1/2. Conclusion: Our results suggest that compound 2b is considered as a promising antiangiogenic agent by targeting VEGF and MMP-9.

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Novel 1,5-diphenyl-6-substituted 1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones induced apoptosis in RKO colon cancer cells

Cited by 5 publications

References 48 publications

Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

Synthesis and Biological Evaluation of New Benzochromenopyrimidines for the Therapy of Colon and Lung Cancer

A new microwave-assisted, three-component reaction of 5-aminopyrazole-4-carboxylates: Selective synthesis of substituted 5-aza-9-deaza-adenines

Design and Synthesis of Novel Thioethers Derived from 1,5-Diphenyl-6- thioxo-6,7-dihydro-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones as Antiangiogenic Agents

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