BIOMAT Database Logo BIOMAT Database Logo

Discovery of novel 2-aryl-4-benzoyl-imidazoles targeting the colchicines binding site in tubulin as potential anticancer agents. 2010

Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, United States.

A series of 2-aryl-4-benzoyl-imidazoles (ABI) was synthesized as a result of structural modifications based on the previous set of 2-aryl-imidazole-4-carboxylic amide (AICA) derivatives and 4-substituted methoxylbenzoyl-aryl-thiazoles (SMART). The average IC(50) of the most active compound (5da) was 15.7 nM. ABI analogues have substantially improved aqueous solubility (48.9 μg/mL for 5ga vs 0.909 μg/mL for SMART-1, 0.137 μg/mL for paclitaxel, and 1.04 μg/mL for combretastatin A4). Mechanism of action studies indicate that the anticancer activity of ABI analogues is through inhibition of tubulin polymerization by interacting with the colchicine binding site. Unlike paclitaxel and colchicine, the ABI compounds were equally potent against multidrug resistant cancer cells and the sensitive parental melanoma cancer cells. In vivo results indicated that 5cb was more effective than DTIC in inhibiting melanoma xenograph tumor growth. Our results suggest that the novel ABI compounds may be developed to effectively treat drug-resistant tumors.

UI MeSH Term Description Entries
D007093 Imidazoles Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D003078 Colchicine A major alkaloid from Colchicum autumnale L. and found also in other Colchicum species. Its primary therapeutic use is in the treatment of gout, but it has been used also in the therapy of familial Mediterranean fever (PERIODIC DISEASE). Colchicine, (+-)-Isomer,Colchicine, (R)-Isomer
D004354 Drug Screening Assays, Antitumor Methods of investigating the effectiveness of anticancer cytotoxic drugs and biologic inhibitors. These include in vitro cell-kill models and cytostatic dye exclusion tests as well as in vivo measurement of tumor growth parameters in laboratory animals. Anticancer Drug Sensitivity Tests,Antitumor Drug Screens,Cancer Drug Tests,Drug Screening Tests, Tumor-Specific,Dye Exclusion Assays, Antitumor,Anti-Cancer Drug Screens,Antitumor Drug Screening Assays,Tumor-Specific Drug Screening Tests,Anti Cancer Drug Screens,Anti-Cancer Drug Screen,Antitumor Drug Screen,Cancer Drug Test,Drug Screen, Anti-Cancer,Drug Screen, Antitumor,Drug Screening Tests, Tumor Specific,Drug Screens, Anti-Cancer,Drug Screens, Antitumor,Drug Test, Cancer,Drug Tests, Cancer,Screen, Anti-Cancer Drug,Screen, Antitumor Drug,Screens, Anti-Cancer Drug,Screens, Antitumor Drug,Test, Cancer Drug,Tests, Cancer Drug,Tumor Specific Drug Screening Tests
D005260 Female Females
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Design, synthesis, and biological evaluation of 1-substituted -2-aryl imidazoles targeting tubulin polymerization as potential anticancer agents.
December 2019, European journal of medicinal chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Design, Synthesis, and Biological Evaluation of Stable Colchicine-Binding Site Tubulin Inhibitors 6-Aryl-2-benzoyl-pyridines as Potential Anticancer Agents.
August 2021, Journal of medicinal chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Discovery of Novel 4-Arylisochromenes as Anticancer Agents Inhibiting Tubulin Polymerization.
October 2018, ACS medicinal chemistry letters,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents.
May 2018, Bioorganic & medicinal chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Imidazoles as potential anticancer agents.
September 2017, MedChemComm,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Indole derivatives targeting colchicine binding site as potential anticancer agents.
October 2023, Archiv der Pharmazie,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Design, synthesis and biological evaluation of novel 5,6,7-trimethoxy-N-aryl-2-styrylquinolin-4-amines as potential anticancer agents and tubulin polymerization inhibitors.
May 2020, Bioorganic chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Discovery of novel 2-aryl-4-bis-amide imidazoles (ABAI) as anti-inflammatory agents for the treatment of inflammatory bowel diseases (IBD).
March 2022, Bioorganic chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Synthesis, biological evaluation and molecular docking studies of aminochalcone derivatives as potential anticancer agents by targeting tubulin colchicine binding site.
August 2018, Bioorganic chemistry,
Jianjun Chen, and Zhao Wang, and Chien-Ming Li, and Yan Lu, and Pavan K Vaddady, and Bernd Meibohm, and James T Dalton, and Duane D Miller, and Wei Li
Discovery and optimization of a series of 2-aryl-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazoles as novel anticancer agents.
June 2012, Journal of medicinal chemistry,
Copied contents to your clipboard!