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In the designed compounds, either a biarylamide or biarylurea moiety or an N-substituted piperazine motif was linked to position 1 of the phthalazine core. The anti-proliferative activity of the synthesised compounds revealed that eight compounds (6b, 6e, 7b, 13a, 13c, 16a, 16d and 17a) exhibited excellent broad spectrum cytotoxic activity in NCI 5-log dose assays against the full 60 cell panel with GI50 values ranging from 0.15 to 8.41 µM. Moreover, the enzymatic assessment of the synthesised compounds against VEGFR-2 tyrosine kinase showed the significant inhibitory activities of the biarylureas (12b, 12c and 13c) with IC50s of 4.4, 2.7 and 2.5 μM, respectively, and with 79.83, 72.58 and 71.6% inhibition of HUVEC at 10 μM, respectively. Additionally, compounds (7b, 13c and 16a) were found to induce cell cycle arrest at S phase boundary. Compound 7b triggered a concurrent increase in cleaved caspase-3 expression level, indicating the apoptotic-induced cell death. [ABSTRACT FROM AUTHOR]

This study involves the synthesis and anticonvulsant evaluation of 1-ethyl-3-hydrazinylquinoxaline-2-(1H)-one ( 8), its chemical confirmations 9 and 10 and certain (1,2,4) triazolo(4,3-a)quinoxalin-4(5H)-one compounds 11, 12, 13, 13a, 13b, 13c, 13d, 13e, 13f, 14, 15, 16. The structure of the synthesized compounds was confirmed chemically by elemental analyses and spectral data (IR, 1H NMR, 13C NMR, and Mass). Docking studies were preformed to all of the synthesized compounds to predict, in a qualitative way, the anticonvulsant activity of the proposed compounds. There is a promising correlation between the results of and the anticonvulsant activity of the synthesized compounds. The highest fitting value was noticed for compounds 9 and 10, which showed the highest anticonvulsant activity. [ABSTRACT FROM AUTHOR]

A series of novel ciprofloxacin (CP) derivatives substituted at the N-4 position with biologically active moieties were designed and synthesised. 14 compounds were 1.02- to 8.66-fold more potent than doxorubicin against T-24 cancer cells. Ten compounds were 1.2- to 7.1-fold more potent than doxorubicin against PC-3 cancer cells. The most potent compounds 6, 7a, 7b, 8a, 9a, and 10c showed significant Topo II inhibitory activity (83–90% at 100 μM concentration). Compounds 6, 8a, and 10c were 1.01- to 2.32-fold more potent than doxorubicin. Compounds 6 and 8a induced apoptosis in T-24 (16.8- and 20.1-fold, respectively compared to control). This evidence was supported by an increase in the level of apoptotic caspase-3 (5.23- and 7.6-fold, sequentially). Both compounds arrested the cell cycle in the S phase in T-24 cancer cells while in PC-3 cancer cells the two compounds arrested the cell cycle in the G1 phase. Molecular docking simulations of compounds 6 and 8a into the Topo II active site rationalised their remarkable Topo II inhibitory activity. [ABSTRACT FROM AUTHOR]

[Display omitted] • Numerous cancer chemotherapeutic drugs target Topo II enzymes. • Selective targeting of Topo II for cancer treatment is an active field in research. • Anthracyclines, epipodophyllotoxins and fluoroquinolones are Topo II inhibitors. • The review summarizes their modes of action, and SARs from 2013 to 2023. • The review highlights the mechanism of action and SARs of new Topo II inhibitors. The DNA topoisomerase enzymes are widely distributed throughout all spheres of life and are necessary for cell function. Numerous antibacterial and cancer chemotherapeutic drugs target the various topoisomerase enzymes because of their roles in maintaining DNA topology during DNA replication and transcription. Agents derived from natural products, like anthracyclines, epipodophyllotoxins and quinolones, have been widely used to treat a variety of cancers. A very active field of fundamental and clinical research is the selective targeting of topoisomerase II enzymes for cancer treatment. This thematic review summarizes the recent advances in the anticancer activity of the most potent topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins and fluoroquinolones) their modes of action, and structure–activity relationships (SARs) organized chronologically in the last ten years from 2013 to 2023. The review also highlights the mechanism of action and SARs of promising new topoisomerase II inhibitors. [ABSTRACT FROM AUTHOR]