Synthesis and biological evaluation of 5,6,7-trimethoxy-1-benzylidene-3,4-dihydro-naphthalen-2-one as tubulin-polymerization inhibitors

Jiang, Jun-Hang; Zheng, Canhui; Wang, Chongqing; Wang, Juan; Tian, Wei; Yang, Chao; Song, Yuelin; Hu, Yujin; Zhu, Jin; Zhou, You‐Yun

doi:10.1016/j.cclet.2015.03.022

Cited by 5 publications

(2 citation statements)

References 19 publications

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“…Combretastatin A-4 (CA-4), which was first isolated from the bark of Combretum caffrum in South African, is a famous natural product for its antitumor effect as a potentially effective vascular disrupting agent (VDA). , The tumor vasculature, which has a close relationship with the growth of tumors, is an attractive target for cancer therapy . To date, VDAs have many advantages in anticancer therapy .…”

Section: Introductionmentioning

confidence: 99%

Tumor Neovasculature-Targeted APRPG-PEG-PDLLA/MPEG-PDLLA Mixed Micelle Loading Combretastatin A-4 for Breast Cancer Therapy

Hao

Peng

Zhang

et al. 2017

ACS Biomater. Sci. Eng.

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Breast cancer has been the first killer among women. In this study, combretastatin A-4 (CA-4) loaded 5-amino acid peptide Ala-Pro-Arg-Pro-Gly (APRPG) modified PEG-PDLLA mixed micelles was developed to target tumor neovasculature for breast cancer therapy. CA-4 is an effective vascular disrupting agent. The APRPG-modified PEG-PDLLA polymer was successfully synthesized and thin-film hydration method was used to prepare APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles. Drug loading capacity (DL), encapsulation efficiency (EE), and the optimized ratio of APRPG-PEG-PDLLA: MPEG-PDLLA for efficient drug loading was investigated. The particle size, zeta potential, morphology, and the crystallographic study were carried out to characterize the micelles. In vitro release study revealed a sustained release of CA-4 from the mixed micelles while compared to free CA-4. Moreover, the cytotoxicity data of blank and drug loaded mixed micelles suggested that the APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles were safe drug carriers and the encapsulated CA-4 remained potent antitumor effect. The cellular uptake study and the in vivo imaging and biodistribution study demonstrated that the APRPG peptide modified mixed micelles has the higher cellular uptake efficiency and could significantly facilitate the accumulation at tumor site. Furthermore, the micelles were slowly extravasated from blood vessels and inhibited embryonic angiogenesis in the transgenic zebrafish model. Consequently, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles group demonstrated a significant inhibition of tumor growth in 4T1 breast cancer model. In short, the CA-4 loaded APRPG-PEG-PDLLA/MPEG-PDLLA mixed micelles might have great potential for breast cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Tumor Neovasculature-Targeted APRPG-PEG-PDLLA/MPEG-PDLLA Mixed Micelle Loading Combretastatin A-4 for Breast Cancer Therapy

Hao

Peng

Zhang

et al. 2017

ACS Biomater. Sci. Eng.

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“…A member of this family, pyrrolo-1,5-benzoxazepine-15 ( Figure 1 E), has shown potent pro-apoptotic activity in a variety of human tumor cell types including liver (Hep-G2), breast (MCF7) and colon (HCT116) cancer cell lines, with minimal toxicity toward normal blood and bone marrow cells [ 9 , 10 ]. A cis-stilbene natural product combretastatin A-4 ( Figure 1 F) is a lead compound of vascular-disrupting agents targeting tumor blood vessels that binds to the colchicine site and exerts potent cytotoxicity, particularly due to having a cis-configuration-linking bridge and two relatively flexible six-membered hydrophobic rings with the appropriate dihedral angle [ 11–13 ].…”

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confidence: 99%

Indole-Fused Benzooxazepines: a New Structural Class of Anticancer Agents

et al. 2017

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Aim:A new series of compounds (1a–16a) bearing indole-fused benzooxazepine was synthesized, characterized and evaluated for anticancer activity.Materials & methods:In this study, all the synthesized compounds were screened via in vitro anticancer testing on Hep-G2 cancer cell line. A computational study was carried out on cancer-related targets including IL-2, IL-6, COX-2 Caspase-3 and Caspase-8.Results:Some of the synthesized compounds effectively controlled the growth of cancerous cells.Conclusion:The most active compounds – 6a, 10a, 13a, 14a and 15a – exemplify notable anticancer profile with GI50 <10 μg/ml. Preliminary structure–activity relationship among the tested compounds can produce an assumption that the electronegative groups at phenyl ring attached with indole-fused benzooxazepine are instrumental for the activity. Molecular docking study showed crucial hydrogen bond and π–π stacking interactions, with good ADMET profiling and molecular dynamic simulation.

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Novel Aldimine‐Type Schiff Bases of 4‐Amino‐5‐[(3,4,5‐trimethoxyphenyl)methyl]‐1,2,4‐triazole‐3‐thione/thiol: Docking Study, Synthesis, Biological Evaluation, and Anti‐Tubulin Activity

Ameri

Khodarahmi

Hassanzadeh

et al. 2016

Archiv der Pharmazie

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The present study was planned to design some novel aldimine-type Schiff bases bearing 3,4,5-trimethoxyphenyl and 1,2,4-triazole-3-thione/thiol as potential tubulin polymerization inhibitors. The obtained results of the molecular docking study using the tubulin complex (PDB code: 1SA0) showed that compounds H-25 and H-26 were well fitted in the colchicine binding site of tubulin with binding energies of -8.68 and -8.40 kcal/mol, respectively, in comparison to the main ligand (-8.20 kcal/mol). In parallel, molecular simulations were also performed on five other 3,4,5-trimethoxyphenyl-containing ligand targets including hsp90, VEGFR2, and human and microbial (Staphylococcus aureus and Candida albicans) dihydrofolate reductase, among which H-17, H-45, H-27, H-02, and H-19 were the most suitable compounds, respectively. Evaluation of the cytotoxic effect of the most efficient compounds of the docking steps (H-25) revealed IC50 values of 12.48 ± 1.10, 4.25 ± 0.22, 3.33 ± 0.31, and 9.71 ± 0.75 µM against the HT1080, HT29, MCF-7, and A549 cell lines, respectively, compared to doxorubicin (12.69 ± 1.23, 6.12 ± 0.47, 3.51 ± 0.32, and 6.40 ± 0.31 µM, respectively). The in vitro tubulin polymerization investigation launched compounds H-25 and H-26 as potent antitubulin agents due to their IC50 values of 0.17 ± 0.01 and 10.93 ± 0.43 µM, respectively.

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Synthesis and biological evaluation of 5,6,7-trimethoxy-1-benzylidene-3,4-dihydro-naphthalen-2-one as tubulin-polymerization inhibitors

Cited by 5 publications

References 19 publications

Tumor Neovasculature-Targeted APRPG-PEG-PDLLA/MPEG-PDLLA Mixed Micelle Loading Combretastatin A-4 for Breast Cancer Therapy

Tumor Neovasculature-Targeted APRPG-PEG-PDLLA/MPEG-PDLLA Mixed Micelle Loading Combretastatin A-4 for Breast Cancer Therapy

Indole-Fused Benzooxazepines: a New Structural Class of Anticancer Agents

Novel Aldimine‐Type Schiff Bases of 4‐Amino‐5‐[(3,4,5‐trimethoxyphenyl)methyl]‐1,2,4‐triazole‐3‐thione/thiol: Docking Study, Synthesis, Biological Evaluation, and Anti‐Tubulin Activity

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