A series of 18 novel 1-indolyl acetate-5-nitroimidazole 3a-3r were designed, synthesized, and evaluated for their in vitro biological activities as potential tubulin polymerization inhibitors. Among these compounds, 3p displayed strong antitumor activity with IC50 of 2.00, 1.05, 0.87 μM against A549, Hela and U251 respectively, and also showed the most potent PLK1 inhibitory activity with IC50 of 2.4 μM. Molecular docking studies within the colchicine binding site of tubulin were in good agreement with the tubulin polymerization inhibitory data and confirmed the importance of the configuration of the synthesized 1-indolyl acetate-5-nitroimidazolefor potential tubulin polymerization inhibitors.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.ejmech.2014.07.082 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Drug-Linker Constructs Bearing Unique Dual-Mechanism Tubulin Binding Payloads Tethered through Cleavable and Non-Cleavable Linkers.
Tetrahedron
February 2025
Department of Chemistry and Biochemistry, Baylor University, One Bear Place, No. 97348, Waco, Texas 76798-7348, United States.
Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels.
View Article and Find Full Text PDFErwinia phage Asesino is a nucleus-forming phage that lacks PhuZ.
Sci Rep
January 2025
School of Biological Sciences, University of California San Diego, La Jolla, CA, 92093, USA.
As nucleus-forming phages become better characterized, understanding their unifying similarities and unique differences will help us understand how they occupy varied niches and infect diverse hosts. All identified nucleus-forming phages fall within the Chimalliviridae family and share a core genome of 68 unique genes including chimallin, the major nuclear shell protein. A well-studied but non-essential protein encoded by many nucleus-forming phages is PhuZ, a tubulin homolog which aids in capsid migration, nucleus rotation, and nucleus positioning.
View Article and Find Full Text PDFAbscisic Acid, Microtubules and Phospholipase D-Solving a Cellular Bermuda Triangle.
Int J Mol Sci
December 2024
Molecular Cell Biology, Joseph Gottlieb Kölreuter Institute for Plant Sciences, Karlsruhe Institute of Technology, Fritz-Haber-Weg 4, 76131 Karlsruhe, Germany.
Rice plants are important food crops that are sensitive to cold stress. Microtubules (MTs) are highly associated with plant response to cold stress. The exogenous application of abscisic acid (ABA) can transiently induce the cold stability of microtubules.
View Article and Find Full Text PDFHippocampal dendritic spines store-operated calcium entry and endoplasmic reticulum content is dynamic microtubule dependent.
Sci Rep
January 2025
Laboratory of Biomedical Imaging and Data Analysis, Institute of Biomedical Systems and Biotechnology, Peter the Great St. Petersburg Polytechnic University, Khlopina St. 11, St. Petersburg, Russia, 194021.
One of the mechanisms of calcium signalling in neurons is store-operated calcium entry (SOCE), which is activated when the calcium concentration in the smooth endoplasmic reticulum (ER) decreases and its protein-calcium sensor STIM (stromal interacting molecule) relocate to the endoplasmic reticulum and plasma membrane junctions, forms clusters and induces calcium entry. In electrically non-excitable cells, STIM1 is coupled with the positive end of a tubulin microtubule through interaction with EB1 (end-binding) protein, which controls its oligomerization, SOCE and participates in ER movement. STIM2 homologue, which is specific for mature hippocampal dendritic spines, is known to interact with EB3 protein, however, not much is known about the role of this interaction in STIM2 clustering or ER trafficking in neurons.
View Article and Find Full Text PDFDesign, synthesis, and structure-activity relationships of five-membered heterocyclic incorporated aryl(alkyl)azoles: From antiproliferative thiazoles to safer anticonvulsant oxadiazoles.
Bioorg Chem
December 2024
Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:
In the current study, a novel series of 1,2,4-oxadiazoles were designed, synthesized, and evaluated for their biological activities. A cell-based antiproliferative screening was accomplished on the newly synthesized 1,2,4-oxadiazoles along with our previously reported aryl(alkyl)azoles (AAAs) containing middle heterocyclic cores thiazole and oxazole. Among the tested compounds, naphthyl- thiazoles demonstrated higher antiproliferative activity and B3 was identified as the most potent compound with IC values in the range of 2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!