Combretastatin A-4 inspired novel 2-aryl-3-arylamino-imidazo-pyridines/pyrazines as tubulin polymerization inhibitors, antimitotic and anticancer agents

MedChemComm ◽  
2014 ◽  
Vol 5 (6) ◽  
pp. 766-782 ◽  
Author(s):  
Nitesh Sanghai ◽  
Vaibhav Jain ◽  
Ranjan Preet ◽  
Somnath Kandekar ◽  
Sarita Das ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Tubulin Polymerization ◽  
Chromosomal Damage ◽  
Tubulin Polymerization Inhibitors

Novel 2-aryl-3-arylamino-imidazo-pyridines/pyrazines that exhibit potent tubulin polymerization inhibition, anticancer activity, anti-migration of cancer cells, chromosomal damage, and apoptosis have been developed.

scholarly journals NBM-HD-1: A Novel Histone Deacetylase Inhibitor with Anticancer Activity

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Wei-Jan Huang ◽  
Yu-Chih Liang ◽  
Shuang-En Chuang ◽  
Li-Ling Chi ◽  
Chi-Yun Lee ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Xenograft Model ◽  
Cyclin B1 ◽  
Dependent Manner ◽  
Cell Cycle Regulators ◽  
Anticancer Activities ◽  
Gene Expressions

HDAC inhibitors (HDACis) have been developed as promising anticancer agents in recent years. In this study, we synthesized and characterized a novel HDACi, termed NBM-HD-1. This agent was derived from the semisynthesis of propolin G, isolated from Taiwanese green propolis (TGP), and was shown to be a potent suppressor of tumor cell growth in human breast cancer cells (MCF-7 and MDA-MB-231) and rat glioma cells (C6), with an IC50ranging from 8.5 to 10.3 μM. Western blot demonstrated that levels of p21(Waf1/Cip1), gelsolin, Ac-histone 4, and Ac-tubulin markedly increased after treatment of cancer cells with NBM-HD-1. After NBM-HD-1 treatment for 1–4 h, p-PTEN and p-AKT levels were markedly decreased. Furthermore, we also found the anticancer activities of NBM-HD-1 in regulating cell cycle regulators. Treatment with NBM-HD-1,p21(Waf1/Cip1)gene expression had markedly increased whilecyclin B1andD1gene expressions had markedly decreased. On the other hand, we found that NBM-HD-1 increased the expressions of tumor-suppressor genep53in a dose-dependent manner. Finally, we showed that NBM-HD-1 exhibited potent antitumor activity in a xenograft model. In conclusion, this study demonstrated that this compound, NBM-HD-1, is a novel and potent HDACi with anticancer activityin vitroandin vivo.

Discovery of new indole-based 1,2,4-triazole derivatives as potent tubulin polymerization inhibitors with anticancer activity

2021 ◽  
Author(s):  
Fang Yang ◽  
Xie-Er Jian ◽  
Lin Chen ◽  
Yu-Feng Ma ◽  
Yu-Xia Liu ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Tubulin Polymerization ◽  
Hybrid Strategy ◽  
Triazole Derivatives ◽  
Tubulin Polymerization Inhibitors ◽  
Nanomolar Range

Thirty-six novel indole-based 1,2,4-triazole derivatives were designed and synthesized through the molecular hybrid strategy. The bioassay results revealed that 9p displayed excellent antiproliferative efficacies in the nanomolar range against HeLa...

ANTICANCER POTENTIAL OF PLANT EXTRACTS FROM RIYADH (SAUDI ARABIA) ON MDA-MB-231 BREAST CANCER CELLS

2018 ◽  
Vol 15 (4) ◽  
pp. 46 ◽  
Author(s):  
Fahd A. Nasr ◽  
Nael Abutaha ◽  
Mohammad Al-Zahrani ◽  
Muhammad Farooq ◽  
Mohammad A Wadaan
Keyword(s):  
Breast Cancer ◽  
Saudi Arabia ◽  
Medicinal Plants ◽  
Traditional Medicine ◽  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Breast Cancer Cells ◽  
Morphological Changes ◽  
Cell Integrity

Background: Medicinal plants have been used in traditional medicine for the treatment of numerous diseases worldwide. There is a dire need for new anticancer agents and plants used in traditional medicine are a particularly useful source. Materials and methods: In this study, extracts of five different plants that grow in the desert of Saudi Arabia were evaluated to assess their cytotoxicity against the MDA-MB-231 breast cancer cell line. Soxhlet extraction was carried out on the leaves and stems using different solvents. The cytotoxicity of these extracts against MDA-MB-231 breast cancer cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The apoptotic cellular morphological changes were observed using inverted and fluorescence microscopes. Results: Our results showed that two of the five different medicinal plants (Rumex vesicarius and Malva parviflora) exhibited strong anticancer activity against the breast cancer cells. Specifically, 2 of the 40 extracts (from the five studied plants) showed promising activity. The chloroform extract of the stem of R. vesicarius (RSV CHCL3) exhibited moderate anticancer activity with a half-maximal inhibitory concentration (IC50) of 230 µg/mL while that of the hexane extract of M. parviflora stems (MPS Hex) was 248 µg/mL. Loss of cell integrity, shrinkage of the cytoplasm, and cell detachment were observed in the extract-treated MDA-MB-231 cells. Conclusion: R. vesicarius and M. parviflora chloroform and n-hexane stem extracts showed significant cytotoxicity against MDA-MB-231 human breast carcinoma cells.

The Structure of MT189-Tubulin Complex Provides Insights into Drug Design

2019 ◽  
Vol 16 (9) ◽  
pp. 1069-1073
Author(s):  
Zhongping Li ◽  
Lingling Ma ◽  
Chengyong Wu ◽  
Tao Meng ◽  
Lanping Ma ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Binding Site ◽  
Complex Structure ◽  
Microtubule Assembly ◽  
Tubulin Polymerization ◽  
Colchicine Binding Site ◽  
Structure Activity ◽  
Tubulin Tyrosine Ligase ◽  
Tubulin Polymerization Inhibitors

Background: Drugs that interfere with microtubule dynamics are used widely in cancer chemotherapy. Microtubules are composed of αβ-tubulin heterodimers, and the colchicine binding site of tubulin is an important pocket for designing tubulin polymerization inhibitors. We have previously designed and synthesized a series of colchicine binding site inhibitors (CBSIs). However, these compounds showed no anticancer activity in vivo. Then, we have used a deconstruction approach to obtain a new derivative MT189, which showed in vivo anticancer activity. Methods: We crystallized a protein complex including two tubulins, one stathmin-like domain of RB3 and one tubulin tyrosine ligase, and soaked MT189 into the crystals. We collected the diffraction data and determined the tubulin-MT189 structure to 2.8 Å. Results: Here, we report the crystal structure of tubulin complexed with MT189, elucidate how the small-molecular agent binds to tubulin and inhibits microtubule assembly, and explain previous results of the structure-activity-relationship studies. Conclusion: The tubulin-MT189 complex structure reveals the interactions between this agent and tubulin and provides insights into the design of new derivatives targeting the colchicine binding site.

scholarly journals Novel 11-Substituted Ellipticines as Potent Anticancer Agents with Divergent Activity against Cancer Cells

2019 ◽  
Vol 12 (2) ◽  
pp. 90 ◽  
Author(s):  
Charlotte M. Miller ◽  
Elaine C. O’Sullivan ◽  
Florence O. McCarthy
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Natural Product ◽  
Anticancer Agents ◽  
Cellular Growth ◽  
Growth Effects

Ellipticines have well documented anticancer activity, in particular with substitution at the 1-, 2-, 6- and 9-positions. However, due to limitations in synthesis and coherent screening methodology the full SAR profile of this anticancer class has not yet been achieved. In order to address this shortfall, we have set out to explore the anticancer activity of this potent natural product by substitution. We currently describe the synthesis of novel 11-substituted ellipticines with two specific derivatives showing potency and diverging cellular growth effects.

scholarly journals Biological activity and interaction mechanism of the diketopiperazine derivatives as tubulin polymerization inhibitors

RSC Advances ◽  
2018 ◽  
Vol 8 (2) ◽  
pp. 1055-1064 ◽  
Author(s):  
Zhenhua Tian ◽  
Yanyan Chu ◽  
Hui Wang ◽  
Lili Zhong ◽  
Mengyan Deng ◽  
...  
Keyword(s):  
Biological Activity ◽  
Anticancer Agents ◽  
Interaction Mechanism ◽  
Tubulin Polymerization ◽  
Tubulin Polymerization Inhibitors

Microtubules are a favorable target for development of anticancer agents.

scholarly journals Potential of Anti-Cancer Activity of Secondary Metabolic Products from Marine Fungi

2021 ◽  
Vol 7 (6) ◽  
pp. 436
Author(s):  
Efaq Noman ◽  
Muhanna Mohammed Al-Shaibani ◽  
Muhammed Adnan Bakhrebah ◽  
Reyad Almoheer ◽  
Mohammed Al-Sahari ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Marine Fungi ◽  
Metabolic Process ◽  
Anticancer Compounds ◽  
Current Review ◽  
Anti Cancer ◽  
Metabolic Products ◽  
Available Information

The promising feature of the fungi from the marine environment as a source for anticancer agents belongs to the fungal ability to produce several compounds and enzymes which contribute effectively against the cancer cells growth. L-asparaginase acts by degrading the asparagine which is the main substance of cancer cells. Moreover, the compounds produced during the secondary metabolic process acts by changing the cell morphology and DNA fragmentation leading to apoptosis of the cancer cells. The current review has analyed the available information on the anticancer activity of the fungi based on the data extracted from the Scopus database. The systematic and bibliometric analysis revealed many of the properties available for the fungi to be the best candidate as a source of anticancer drugs. Doxorubicin, actinomycin, and flavonoids are among the primary chemical drug used for cancer treatment. In comparison, the most anticancer compounds producing fungi are Aspergillus niger, A. fumigatus A. oryzae, A. flavus, A. versicolor, A. terreus, Penicillium citrinum, P. chrysogenum, and P. polonicum and have been used for investigating the anticancer activity against the uterine cervix, pancreatic cancer, ovary, breast, colon, and colorectal cancer.

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