Design, synthesis and antiproliferative evaluation of new tricyclic fused thiazolopyrimidines targeting topoisomerase II: Molecular docking and apoptosis inducing activity

Nemr, Mohamed T. M.; Sonousi, Amr; Marzouk, Adel A.

doi:10.1016/j.bioorg.2020.104446

Cited by 30 publications

(10 citation statements)

References 27 publications

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“…This challenge lies in the difficulty to discover novel selective agents that inhibit the proliferation of tumor cells without being toxic to normal cells. [1][2][3][4] According to GLO-BOCAN, 2020 estimation, about 19.3 million cancer cases and 10 million cancer deaths are estimated to occur worldwide in 2020. Breast cancer (BC) is one of the most commonly diagnosed and the second leading cause of cancer related deaths in females.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agents via carbonic anhydrase IX inhibition

et al. 2021

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Section: Introductionmentioning

confidence: 99%

Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agents via carbonic anhydrase IX inhibition

et al. 2021

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“…Previous studies have identified several acridone derivatives as TopoII inhibitors and DNA intercalator with cell cycle arrest and apoptosis [56,57]. Furthermore, in Egypt, Nemr et al [58], and Nemr and AboulMagd [59], worked on a novel series of thiazolopyrimidines and fused thiazolopyrimidines, screened for anticancer activity against 60 human cancer cell lines. They found Ethyl 4-(4-bromophenyl)-2-imino-9-(3,4,5-trimethoxyphenyl)-7-phenyl-1,2dihydro-9H-pyrimido[4',5':4,5]thiazolo[3,2-a]pyrimidine-8-carboxylate, and Ethyl 3-(4chlorophenyl)-5-(4-chlorophenyl)-7-phenyl-5H-thiazolo-[3,2-a] pyrimidine-6-carboxylate hydrobromide, to be the potent inhibitors on renal cell line (A-498) and induce cell cycle arrest at G2/M phase leading to cell proliferation inhibition and apoptosis, and that their fused derivative both showed potent TopoII inhibitory activity with IC50 slightly higher than that of standard drug, doxorubicin.…”

Section: -(4-(acridin-9ylamino)-phenyl)-1h-123-triazol-1-yl)-n-hydrox...mentioning

confidence: 99%

A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

Okoro¹,

Fatoki²

2022

Preprint

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Several reviews of inhibitors of topoisomerase II literature have been published covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, that are further subdivided into poisons and catalytic inhibitors. Whereas most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including development of multi drug resistance. As a result, we are beginning to see a gradual paradigm shift towards a non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review will describe some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as leads for optimization and development to new potent, safe and selective agents for the treatment of cancer.

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“…Among these features, methoxy groups, ethyl carboxylate moiety, and amide linkers were discovered to boost antitumor activity 20–23 . On the other hand, a series of 3-oxo thiazolo[3,2- a ]pyrimidines (III) were found to be significant topoisomerase II inhibitors 24 . Furthermore, thiazolo[3,2- a ]pyrimidines (IV) have been reported to have excellent topoisomerase II inhibitory activity 25 ( Figure 2 ).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2- a ] pyrimidines as topoisomerase II inhibitors

El‐Zoghbi

El‐Sebaey

Al-Ghulikah

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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New thiazolopyrimidine derivatives 2, 3a-d, 4a-c, 5, 6a-c, and 7a,b were synthesised. All prepared compounds were evaluated by MTT cytotoxicity assay against three human tumour cell lines. Compounds 3c, 3d, 4c, 6a, 6b, and 7b exhibited potent to strong anticancer activity that was nearly comparable or superior to Doxorubicin. Compounds exhibiting significant cytotoxicity were further selected to study their inhibitory activity on the Topo II enzyme. Compound 4c was the most potent Topo II inhibitor with an IC 50 value of 0.23 ± 0.01 µM, which was 1.4-fold and 3.6-fold higher than the IC 50 values of Etoposide and Doxorubicin. Furthermore, compound 4c showed significant cell cycle disruption and apoptosis on A549 cells compared to control cells. Molecular docking of the most active compounds illustrated proper fitting to the Topo II active site, suggesting that our designed compounds are promising candidates for the development of effective anticancer agents acting through Topo II inhibition.

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Design, synthesis and antiproliferative evaluation of new tricyclic fused thiazolopyrimidines targeting topoisomerase II: Molecular docking and apoptosis inducing activity

Cited by 30 publications

References 27 publications

Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agents via carbonic anhydrase IX inhibition

Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agents via carbonic anhydrase IX inhibition

A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

Design, synthesis, docking, and anticancer evaluations of new thiazolo[3,2- a ] pyrimidines as topoisomerase II inhibitors

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