Recent Advances in Combretastatin A-4 Inspired Inhibitors of Tubulin Polymerization-An Update

2022 ◽  
Vol 29 ◽  
Author(s):  
Sultan Nacak Baytas
Keyword(s):  
Drug Targets ◽  
Therapeutic Strategies ◽  
Tubulin Polymerization ◽  
Molecular Chemistry ◽  
Microtubule Polymerization ◽  
Colchicine Binding Site ◽  
Microtubule Targeting Agents ◽  
Genomics And Proteomics ◽  
Potential Drug Targets ◽  
Structural Simplicity

Abstract: Cancer is one of the leading causes of fatality and mortality worldwide. Investigations on developing therapeutic strategies for cancer are supported throughout the world. The massive achievements in molecular sciences involving biochemistry, molecular chemistry, medicine, and pharmacy, and high throughput techniques such as genomics and proteomics have helped to create new potential drug targets for cancer treatment. Microtubules are very attractive targets for cancer therapy because of the crucial roles they play in cell division. In recent years, lots of efforts have been put into the identification of new microtubule-targeting agents (MTAs) in anticancer therapy. Combretastatin A-4 (CA-4) is a natural compound that binds to microtubules’ colchicine binding site and inhibits microtubule polymerization. Due to CA-4’s structural simplicity, many analogs have been synthesized. This article summarizes the new molecule development efforts to reach CA-4 analogs by modifications on its pharmacophore groups, published since 2015.

scholarly journals A Conserved Machinery Underlies the Synthesis of a Chitosan Layer in the Candida Chlamydospore Cell Wall

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Leo D. Bemena ◽  
Kyunghun Min ◽  
James B. Konopka ◽  
Aaron M. Neiman
Keyword(s):  
Cell Wall ◽  
Cell Walls ◽  
Drug Targets ◽  
Therapeutic Strategies ◽  
Effective Strategy ◽  
Fungal Cell ◽  
Detailed Understanding ◽  
Cell Wall Assembly ◽  
Wall Assembly ◽  
Potential Drug Targets

The cell wall is the interface between the fungal cell and its environment and disruption of cell wall assembly is an effective strategy for antifungal therapies. Therefore, a detailed understanding of how cell walls form is critical to identify potential drug targets and develop therapeutic strategies.

Wide Range Logarithmic Gradient Formation for Cell Response

2011 ◽  
Author(s):  
Morgan Hamon ◽  
Kirn Cramer ◽  
Sachin Jambovane ◽  
Jing Dai ◽  
Ali Khademhosseini ◽  
...  
Keyword(s):  
Drug Targets ◽  
Combinatorial Synthesis ◽  
New Drugs ◽  
Drug Discovery Process ◽  
Drug Candidates ◽  
Genomics And Proteomics ◽  
Wide Range ◽  
Gradient Formation ◽  
Human Genome Sequencing ◽  
Potential Drug Targets

Recently, the number of potential drug targets has dramatically increased because of the recent completion of the human genome sequencing and the progress in genomics and proteomics. In parallel, the number of new drugs for those targets has also been increased due to the use of combinatorial synthesis and the increased access to natural molecules [1]. However, this has not increased consequently the number of approved new drugs delivered to patients [2]. Indeed the drug discovery process is still limited by numbers of challenges; among them the need to analyze in more rapid and accurate manner precious sample of drug candidates.

Proteomic and Bioinformatic Analysis of Trypanosoma cruzi Chemotherapy and Potential Drug Targets: New Pieces for an Old Puzzle

2014 ◽  
Vol 15 (3) ◽  
pp. 255-271 ◽  
Author(s):  
Rubem Sadok Menna-Barreto ◽  
Kele Belloze ◽  
Jonas Perales ◽  
Floriano Silva-Jr
Keyword(s):  
Trypanosoma Cruzi ◽  
Drug Targets ◽  
Bioinformatic Analysis ◽  
Potential Drug ◽  
Potential Drug Targets

Synthesis, Anti-proliferative Evaluation, and Molecular Docking Studies of 3-(alkylthio)-5,6-diaryl-1,2,4-triazines as Tubulin Polymerization Inhibitors

2019 ◽  
Vol 16 (11) ◽  
pp. 1194-1201 ◽  
Author(s):  
Farhad Saravani ◽  
Ebrahim Saeedian Moghadam ◽  
Hafezeh Salehabadi ◽  
Seyednasser Ostad ◽  
Morteza Pirali Hamedani ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Cytotoxic Activity ◽  
Binding Site ◽  
Cell Line ◽  
Cell Lines ◽  
Tubulin Polymerization ◽  
Adenocarcinoma Cell Line ◽  
Adenocarcinoma Cell ◽  
Colchicine Binding Site ◽  
Anti Cancer

Background: The role of microtubules in cell division and signaling, intercellular transport, and mitosis has been well known. Hence, they have been targeted for several anti-cancer drugs. Methods: A series of 3-(alkylthio)-5,6-diphenyl-1,2,4-triazines were prepared and evaluated for their cytotoxic activities in vitro against three human cancer cell lines; human colon carcinoma cells HT-29, human breast adenocarcinoma cell line MCF-7, human Caucasian gastric adenocarcinoma cell line AGS as well as fibroblast cell line NIH-3T3 by MTT assay. Docking simulation was performed to insert these compounds into the crystal structure of tubulin at the colchicine binding site to determine a probable binding model. Compound 5d as the most active compound was selected for studying of microtubule disruption. Results: Compound 5d showed potent cytotoxic activity against all cell lines. The molecular modeling study revealed that some derivatives of triazine strongly bind to colchicine binding site. The tubulin polymerization assay kit showed that the cytotoxic activity of 5d may be related to inhibition of tubulin polymerization. Conclusion: The cytotoxicity and molecular modeling study of the synthesized compounds with their inhibition activity in tubulin polymerization demonstrate the potential of triazine derivatives for development of new anti-cancer agents.

Structure, Function and Interactions of Tau: Particular Focus on Potential Drug Targets for the Treatment of Tauopathies

2018 ◽  
Vol 17 (5) ◽  
pp. 325-337 ◽  
Author(s):  
Hojjat Borna ◽  
Kasim Assadoulahei ◽  
Gholamhossein Riazi ◽  
Asghar Beigi Harchegani ◽  
Alireza Shahriary
Keyword(s):  
Tau Protein ◽  
Drug Targets ◽  
Brain Injuries ◽  
Potential Drug ◽  
Microtubule Network ◽  
Wide Range ◽  
Potential Risk Factors ◽  
Range Of Functions ◽  
Potential Drug Targets

Background & Objective: Neurodegenrative diseases are among the most widespread lifethreatening disorders around the world in elderly ages. The common feature of a group of neurodegenerative disorders, called tauopathies, is an accumulation of microtubule associated protein tau inside the neurons. The exact mechanism underlying tauopathies is not well-understood but several factors such as traumatic brain injuries and genetics are considered as potential risk factors. Although tau protein is well-known for its key role in stabilizing and organization of axonal microtubule network, it bears a broad range of functions including DNA protection and participation in signaling pathways. Moreover, the flexible unfolded structure of tau facilitates modification of tau by a wide range of intracellular enzymes which in turn broadens tau function and interaction spectrum. The distinctive properties of tau protein concomitant with the crucial role of tau interaction partners in the progression of neurodegeneration suggest tau and its binding partners as potential drug targets for the treatment of neurodegenerative diseases. Conclusion: This review aims to give a detailed description of structure, functions and interactions of tau protein in order to provide insight into potential therapeutic targets for treatment of tauopathies.

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