27785-54-2

Upstream product

• 19012-03-4 N-methyl-3-formylindole 
• 99-91-2 para-chloroacetophenone 
• 120-72-9 indole 
• 487-89-8 Indole-3-carboxaldehyde 
• 22883-31-4 1-(4''-chloro-phenyl)-3-(1H-indol-3-yl)-prop-2-en-1-one 
• 74-88-4 methyl iodide 

Downstream Products

• 119549-99-4 1-(4-Chloro-phenyl)-3-(1-methyl-1H-indol-3-yl)-3-[1,2,4]triazol-1-yl-propan-1-one 

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 and Biological Evaluation of 1-Methyl-1H-indole–Pyrazoline Hybrids as Potential Tubulin Polymerization Inhibitors

A series of 1-methyl-1H-indole–pyrazoline hybrids were designed, synthesized, and biologically evaluated as potential tubulin polymerization inhibitors. Among them, compound e19 [5-(5-bromo-1-methyl-1H-indol-3-yl)-3-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carboxamide] showed the most potent inhibitory effect on tubulin assembly (IC50=2.12 μm) and in vitro growth inhibitory activity against a panel of four human cancer cell lines (IC50values of 0.21–0.31 μm). Further studies confirmed that compound e19 can induce HeLa cell apoptosis, cause cell-cycle arrest in G2/M phase, and disrupt the cellular microtubule network. These studies, along with molecular docking and 3D-QSAR modeling, provide an important basis for further optimization of compound e19 as a potential anticancer agent.

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.

SYNTHESIS OF SOME INDOLYL-TRIAZOLYL-PROPANONE AND -PROPANOL DERIVATIVES, I

3-(3-Indolyl)-3-(1,2,4-triazolyl)-1-phenylpropan-1-ones and -1-ols were synthesized for tests as herbicides.