27664-11-5

Upstream product

• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 38470-69-8 3-(1'H-indol-3'-yl)-1-(4-methoxyphenyl)-prop-2-en-1-one 
• 74-88-4 methyl iodide 
• 487-89-8 Indole-3-carboxaldehyde 
• 19012-03-4 N-methyl-3-formylindole 

Downstream Products

• 490023-03-5 1-(4-methoxyphenyl)-2-(1-N-methyl-3-indolyl)cyclopropyl ketone 

Relevant academic research and scientific papers

Angiogenesis and anti-leukaemia activity of novel indole derivatives as potent colchicine binding site inhibitors

The screened compound DYT-1 from our in-house library was taken as a lead (inhibiting tubulin polymerisation: IC50=25.6 μM, anti-angiogenesis in Zebrafish: IC50=38.4 μM, anti-proliferation against K562 and Jurkat: IC50=6.2 and 7.9 μM, respectively). Further investigation of medicinal chemistry conditions yielded compound 29e (inhibiting tubulin polymerisation: IC50=4.8 μM and anti-angiogenesis in Zebrafish: IC50=3.6 μM) based on tubulin and zebrafish assays, which displayed noteworthily nanomolar potency against a variety of leukaemia cell lines (IC50= 0.09–1.22 μM), especially K562 cells where apoptosis was induced. Molecular docking, molecular dynamics (MD) simulation, radioligand binding assay and cellular microtubule networks disruption results showed that 29e stably binds to the tubulin colchicine site. 29e significantly inhibited HUVEC tube formation, migration and invasion in?vitro. Anti-angiogenesis in?vivo was confirmed by zebrafish xenograft. 29e also prominently blocked K562 cell proliferation and metastasis in blood vessels and surrounding tissues of the zebrafish xenograft model. Together with promising physicochemical property and metabolic stability, 29e could be considered an effective anti-angiogenesis and -leukaemia drug candidate that binds to the tubulin colchicine site.

Synthesis, biological evaluation and molecular docking studies of novel 1-(4,5-dihydro-1Hpyrazol-1-yl)ethanone-containing 1-methylindol derivatives as potential tubulin assembling inhibitors

A series of novel compounds (6a-6v) containing 1-methylindol and 1-(4,5-dihydro-1H-pyrazol-1-yl) ethanone skeletons were designed, synthesized and biologically evaluated as potential tubulin polymerization inhibitors and anticancer agents. Among them, compound 6q showed the most potent tubulin polymerization inhibitory activity (IC50 = 1.98 mM) and in vitro growth inhibitory activity against A549, MCF-7 and HepG2 cell lines, with IC50 values of 0.15 mM, 0.17 mM, and 0.25 mM respectively, comparable to the positive control. Furthermore, compound 6q was a potent inducer of apoptosis in A549 cells and it had typical cellular effects for microtubule interacting agents, causing arrest of the cell cycle in the G2/M phase. Confocal microscopy assay and molecular docking results further demonstrated that 6q could bind tightly to the colchicine site of tubulin and act as an anti-tubulin agent. These studies, along with 3D-QSAR modeling provided an important basis for further optimization of compound 6q as a potential anticancer agent.

Investigation of chalcones as selective inhibitors of the breast cancer resistance protein: Critical role of methoxylation in both inhibition potency and cytotoxicity

ABCG2 plays a major role in anticancer-drug efflux and related tumor multidrug resistance. Potent and selective ABCG2 inhibitors with low cytotoxicity were investigated among a series of 44 chalcones and analogues (1,3-diarylpropenones), by evaluating their inhibitory effect on the transport of mitoxantrone, a known ABCG2 substrate. Six compounds producing complete inhibition with IC50 values below 0.5 μM and high selectivity for ABCG2 were identified. The number and position of methoxy substituents appeared to be critical for both inhibition and cytotoxicity. The best compounds, with potent inhibition and low toxicity, contained an N-methyl-1-indolyl (compound 38) or a 6′-hydroxyl-2′,4′-dimethoxy-1-phenyl (compound 27) moiety (A-ring) and two methoxy groups at positions 2 and 6 of the 3-phenyl moiety (B-ring). Methoxy substitution contributed to inhibition at positions 3 and 5, but had a negative effect at position 4. Finally, methoxy groups at positions 3, 4, and 5 of the B-ring markedly increased cytotoxicity and, therefore, should be avoided.

Synthesis and biological evaluation of indolyl chalcones as antitumor agents

A series of indolyl chalcones were synthesized and evaluated in vitro for their anticancer activity against three human cancer cell lines. Compounds 3b-d, 3h, 3j, 3l, 3m, 4g, and 4j showed significant cytotoxicity, particularly, indolyl chalcones 3l and 3