FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4384341051> ?p ?o ?g. }

• W4384341051 endingPage "1000" @default.
• W4384341051 startingPage "1000" @default.
• W4384341051 abstract "A series of novel 3-(prop-1-en-2-yl)azetidin-2-one, 3-allylazetidin-2-one and 3-(buta-1,3-dien-1-yl)azetidin-2-one analogues of combretastatin A-4 (CA-4) were designed and synthesised as colchicine-binding site inhibitors (CBSI) in which the ethylene bridge of CA-4 was replaced with a β-lactam (2-azetidinone) scaffold. These compounds, together with related prodrugs, were evaluated for their antiproliferative activity, cell cycle effects and ability to inhibit tubulin assembly. The compounds demonstrated significant in vitro antiproliferative activities in MCF-7 breast cancer cells, particularly for compounds 9h, 9q, 9r, 10p, 10r and 11h, with IC50 values in the range 10-33 nM. These compounds were also potent in the triple-negative breast cancer (TBNC) cell line MDA-MB-231, with IC50 values in the range 23-33 nM, and were comparable with the activity of CA-4. The compounds inhibited the polymerisation of tubulin in vitro, with significant reduction in tubulin polymerization, and were shown to interact at the colchicine-binding site on tubulin. Flow cytometry demonstrated that compound 9q arrested MCF-7 cells in the G2/M phase and resulted in cellular apoptosis. The antimitotic properties of 9q in MCF-7 human breast cancer cells were also evaluated, and the effect on the organization of microtubules in the cells after treatment with compound 9q was observed using confocal microscopy. The immunofluorescence results confirm that β-lactam 9q is targeting tubulin and resulted in mitotic catastrophe in MCF-7 cells. In silico molecular docking supports the hypothesis that the compounds interact with the colchicine-binding domain of tubulin. Compound 9q is a novel potent microtubule-destabilising agent with potential as a promising lead compound for the development of new antitumour agents." @default.
• W4384341051 created "2023-07-15" @default.
• W4384341051 creator A5007312741 @default.
• W4384341051 creator A5008119223 @default.
• W4384341051 creator A5011894823 @default.
• W4384341051 creator A5027097334 @default.
• W4384341051 creator A5029287111 @default.
• W4384341051 creator A5061704800 @default.
• W4384341051 creator A5066223674 @default.
• W4384341051 creator A5073924686 @default.
• W4384341051 creator A5075042666 @default.
• W4384341051 creator A5081602937 @default.
• W4384341051 date "2023-07-13" @default.
• W4384341051 modified "2023-09-30" @default.
• W4384341051 title "Antiproliferative and Tubulin-Destabilising Effects of 3-(Prop-1-en-2-yl)azetidin-2-Ones and Related Compounds in MCF-7 and MDA-MB-231 Breast Cancer Cells" @default.
• W4384341051 cites W175465163 @default.
• W4384341051 cites W1857872584 @default.
• W4384341051 cites W1918363244 @default.
• W4384341051 cites W1963746791 @default.
• W4384341051 cites W1966726954 @default.
• W4384341051 cites W1968893104 @default.
• W4384341051 cites W1969360633 @default.
• W4384341051 cites W1977010953 @default.
• W4384341051 cites W1979859900 @default.
• W4384341051 cites W1987361445 @default.
• W4384341051 cites W1994560457 @default.
• W4384341051 cites W1998693301 @default.
• W4384341051 cites W2019645002 @default.
• W4384341051 cites W2022546029 @default.
• W4384341051 cites W2027542963 @default.
• W4384341051 cites W2032864619 @default.
• W4384341051 cites W2036124984 @default.
• W4384341051 cites W2039098974 @default.
• W4384341051 cites W2053996189 @default.
• W4384341051 cites W2054651663 @default.
• W4384341051 cites W2056944384 @default.
• W4384341051 cites W2059205366 @default.
• W4384341051 cites W2064571598 @default.
• W4384341051 cites W2070835985 @default.
• W4384341051 cites W2074738520 @default.
• W4384341051 cites W2075518165 @default.
• W4384341051 cites W2087360776 @default.
• W4384341051 cites W2092352405 @default.
• W4384341051 cites W2101547779 @default.
• W4384341051 cites W2117036496 @default.
• W4384341051 cites W2118757087 @default.
• W4384341051 cites W2130170373 @default.
• W4384341051 cites W2132454074 @default.
• W4384341051 cites W2136200032 @default.
• W4384341051 cites W2141011226 @default.
• W4384341051 cites W2146730043 @default.
• W4384341051 cites W2148626454 @default.
• W4384341051 cites W2160365238 @default.
• W4384341051 cites W2164660906 @default.
• W4384341051 cites W2232427988 @default.
• W4384341051 cites W2252527010 @default.
• W4384341051 cites W2279758197 @default.
• W4384341051 cites W2319474860 @default.
• W4384341051 cites W2331786801 @default.
• W4384341051 cites W2333842658 @default.
• W4384341051 cites W2334888878 @default.
• W4384341051 cites W2416421359 @default.
• W4384341051 cites W2461240895 @default.
• W4384341051 cites W2492085329 @default.
• W4384341051 cites W2523277769 @default.
• W4384341051 cites W2548252468 @default.
• W4384341051 cites W2573197589 @default.
• W4384341051 cites W2589726745 @default.
• W4384341051 cites W2594226370 @default.
• W4384341051 cites W2747351216 @default.
• W4384341051 cites W2773056962 @default.
• W4384341051 cites W2774836366 @default.
• W4384341051 cites W2806574348 @default.
• W4384341051 cites W2888460025 @default.
• W4384341051 cites W2911464255 @default.
• W4384341051 cites W2911743954 @default.
• W4384341051 cites W2912532602 @default.
• W4384341051 cites W2915598149 @default.
• W4384341051 cites W2916822761 @default.
• W4384341051 cites W2940123959 @default.
• W4384341051 cites W2950442770 @default.
• W4384341051 cites W2950716575 @default.
• W4384341051 cites W2953024891 @default.
• W4384341051 cites W2978692413 @default.
• W4384341051 cites W2982197835 @default.
• W4384341051 cites W2996972660 @default.
• W4384341051 cites W3003945322 @default.
• W4384341051 cites W3016171724 @default.
• W4384341051 cites W3017005254 @default.
• W4384341051 cites W3033128710 @default.
• W4384341051 cites W3037527187 @default.
• W4384341051 cites W3088806729 @default.
• W4384341051 cites W3105871111 @default.
• W4384341051 cites W3109748527 @default.
• W4384341051 cites W3127110282 @default.
• W4384341051 cites W3128646645 @default.
• W4384341051 cites W3129858152 @default.
• W4384341051 cites W3161194413 @default.

• next