4,578 results match your criteria microtubule polymerization

Inhibitor of DNA binding 2 (Id2) mediates microtubule polymerization in the brain by regulating αK40 acetylation of α-tubulin.

Cell Death Discov 2021 Sep 21;7(1):257. Epub 2021 Sep 21.

Department of Molecular Cell Biology, University School of Medicine, 16419, Suwon, Korea.

Acetylation of α-tubulin lysine 40 (αK40) contributes to microtubule (MT) stability and is essential for neuronal development and function, whereas excessive αK40 deacetylation is observed in neurodegenerative disorders including Alzheimer's disease (AD). Here we identified inhibitor of DNA binding 2 (Id2) as a novel MT-binding partner that interacts with α-tubulin and enhances αK40 acetylation, leading to MT polymerization in the neurons. Commensurate with our finding that the low levels of Id2 expression along with a reduced αK40 acetylation in the postmortem human AD patient and 5X-FAD, AD model mice brain, Id2 upregulation in the hippocampus of 5X-FAD, which exhibit high levels of Sirt2 expression, increased αK40 acetylation and reconstitutes axon growth. Read More

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September 2021

Busulfan impairs blood-testis barrier and spermatogenesis by increasing noncollagenous 1 domain peptide via matrix metalloproteinase 9.

Andrology 2021 Sep 18. Epub 2021 Sep 18.

Department of Biochemistry and Molecular Biology, College of Life Science, China Medical University, Shen Yang, 110122, China.

Backgrounds: Sterility induced by anti-cancer treatments has caused significant concern, yet the mechanism and treatment exploration are little for male infertility after cancer therapy. Busulfan (BU), the antineoplastic that widely applied before bone marrow transplantation, was known to induce male reproductive disorder.

Objectives: To investigate the effect of busulfan on blood-testis barrier (BTB) function in adult rats and determine whether noncollagenous 1 (NC1) domain peptide, the biologically active fragment proteolyzed from the collagen α3 chain (IV) by matrix metalloproteinase 9 (MMP-9), was involved during this process. Read More

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September 2021

Design, synthesis, biological evaluation, and molecular docking of new benzofuran and indole derivatives as tubulin polymerization inhibitors.

Drug Dev Res 2021 Sep 15. Epub 2021 Sep 15.

Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Giza, Egypt.

Microtubules and the mitotic spindle have become an important target for cancer treatment due to their critical role in cell division. In this work, a novel series of benzofuran and indole derivatives were designed and synthesized, to be evaluated as tubulin polymerization inhibitors. 2-Acetylbenzofuran derivatives 1a,b and 3-acetylindole 1c were condensed with Wittig reagents 2a-d and Wittig-Horner reagents 3a-e to afford the respective 2-ethylidene derivatives 5a-j and 7a-e. Read More

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September 2021

A new class of cytotoxic agents targets tubulin and disrupts microtubule dynamics.

Bioorg Chem 2021 Aug 30;116:105297. Epub 2021 Aug 30.

Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, 2801, W. Bancroft Street, Toledo, OH-43606, USA. Electronic address:

Despite the advances in treatment strategies, cancer is still the second leading cause of death in the USA. A majority of the currently used cancer drugs have limitations in their clinical use due to poor selectivity, toxic side effects and multiple drug resistance, warranting the development of new anticancer drugs of different mechanisms of action. Here we describe the design, synthesis and initial biological evaluation of a new class of antimitotic agents that modulate tubulin polymerization. Read More

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Inhibition of nitric oxide production enhances the activity of facial nerve tubulin polymerization and the ability of tau to promote microtubule assembly after neurorrhaphy.

Neurochem Int 2021 Sep 9;150:105183. Epub 2021 Sep 9.

Department of Anatomy, Tzu Chi University, No. 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan; Master Program in Medical Physiology, Tzu Chi University, No. 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan. Electronic address:

We previously reported that inhibition of nitric oxide (NO) production promotes rat reconnected facial nerve regeneration. However, the underlying mechanism is obscure. Microtubule assembly is known to be essential to axon regeneration; nevertheless, tubulins and microtubule-associated proteins (MAPs) have been demonstrated as targets for NO and peroxynitrite. Read More

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September 2021

Identification of novel microtubule inhibitors effective in fission yeast and human cells and their effects on breast cancer cell lines.

Open Biol 2021 Sep 8;11(9):210161. Epub 2021 Sep 8.

Laboratory of Yeast Genetics and Cell Biology, Rockefeller University, New York, NY 10065, USA.

Microtubules are critical for a variety of cellular processes such as chromosome segregation, intracellular transport and cell shape. Drugs against microtubules have been widely used in cancer chemotherapies, though the acquisition of drug resistance has been a significant issue for their use. To identify novel small molecules that inhibit microtubule organization, we conducted sequential phenotypic screening of fission yeast and human cells. Read More

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September 2021

Reversed-phase high-performance liquid chromatography: A fast and efficient analytical method to quantify docetaxel-loaded pegylated liposomes in release study.

J Sep Sci 2021 Sep 7. Epub 2021 Sep 7.

School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, São Paulo, Brazil.

Docetaxel is an anticancer that belongs to the family of taxanes and acts in the inhibition of cell proliferation through the polymerization of microtubules. The aim of this study was the development and validation of a fast method by reversed-phase high-performance liquid chromatography for quantitative analysis of docetaxel encapsulated in pegylated liposomes. The analytical method was validated for the following recognized specifications: system suitability, precision (repeatability and intermediate precision), linearity, accuracy, selectivity, detection and quantification limits, and robustness. Read More

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September 2021

Indole derivatives (2010-2020) as versatile tubulin inhibitors: synthesis and structure-activity relationships.

Future Med Chem 2021 Sep 1. Epub 2021 Sep 1.

Department of Chemistry, School of Chemical & Lifescience, Jamia Hamdard, New Delhi, 110062, India.

Tubulin inhibitors are conjugates that interfere with the dynamic equilibrium of the polymerization and depolymerization of microtubules. Among all the reported conjugates, indole moiety is one of the most significant classes for the development of new drug candidates for cancer therapy. Due to their presence in a wide range of natural as well as synthetic antitubulin agents, indole has become a versatile scaffold in research, and various synthetic and semisynthetic indole-based antitubulin agents have been identified and reported. Read More

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September 2021

Conformational changes in tubulin upon binding cryptophycin-52 reveal its mechanism of action.

J Biol Chem 2021 Aug 28;297(4):101138. Epub 2021 Aug 28.

Protein Expression Laboratory, NIAMS, National Institutes of Health, Bethesda, Maryland, USA. Electronic address:

Cryptophycin-52 (Cp-52) is potentially the most potent anticancer drug known, with IC values in the low picomolar range, but its binding site on tubulin and mechanism of action are unknown. Here, we have determined the binding site of Cp-52, and its parent compound, cryptophycin-1, on HeLa tubulin, to a resolution of 3.3 Å and 3. Read More

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Design, synthesis and biological evaluation of novel acridine and quinoline derivatives as tubulin polymerization inhibitors with anticancer activities.

Bioorg Med Chem 2021 Aug 23;46:116376. Epub 2021 Aug 23.

School of Pharmaceutical Sciences, Guangdong Provincial Key Laboratory of New Drug Screening, Southern Medical University, Guangzhou 510515, China. Electronic address:

A series of acridine and quinoline derivatives were designed and synthesized based on our previous work as novel tubulin inhibitors targeting the colchicine binding site. Among them, compound 3b exhibited the highest antiproliferative activity with an IC of 261 nM against HepG-2 cells (the most sensitive cell line). In addition, compound 3b was able to suppress the formation of HepG-2 colonies. Read More

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Discovery of novel tubulin/HDAC dual-targeting inhibitors with strong antitumor and antiangiogenic potency.

Eur J Med Chem 2021 Aug 19;225:113790. Epub 2021 Aug 19.

Henan provincial key laboratory of children's genetics and metabolic diseases, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou University, Zhengzhou, 450018, China. Electronic address:

A novel series of cis-diphenylethene and benzophenone derivatives as tubulin/HDAC dual-targeting inhibitors were designed and synthesized. Among them, compound 28g exhibited the most potent antiproliferative activities against six different human cancer cell lines, 28g could not only inhibited tubulin polymerization, disrupted cellular microtubule networks but also selectively inhibited class IIa HDACs, especially HDAC7 activity. Further molecular docking demonstrated 28g could occupy the binding pockets of tubulin and HDAC7 meanwhile. Read More

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Cytoskeletal Arrest: An Anoxia Tolerance Mechanism.

Metabolites 2021 Aug 23;11(8). Epub 2021 Aug 23.

Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada.

Polymerization of actin filaments and microtubules constitutes a ubiquitous demand for cellular adenosine-5'-triphosphate (ATP) and guanosine-5'-triphosphate (GTP). In anoxia-tolerant animals, ATP consumption is minimized during overwintering conditions, but little is known about the role of cell structure in anoxia tolerance. Studies of overwintering mammals have revealed that microtubule stability in neurites is reduced at low temperature, resulting in withdrawal of neurites and reduced abundance of excitatory synapses. Read More

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Application of ensemble pharmacophore-based virtual screening to the discovery of novel antimitotic tubulin inhibitors.

Comput Struct Biotechnol J 2021 3;19:4360-4372. Epub 2021 Aug 3.

Laboratorio de Química Orgánica y Farmacéutica, Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug is available. The colchicine site is composed of three interconnected sub-pockets that fit their ligands and modify others' preference, making the design of molecular hybrids (that bind to more than one sub-pocket) a difficult task. Read More

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Discovery of Novel Anti-Breast-Cancer Inhibitors by Synergistically Antagonizing Microtubule Polymerization and Aryl Hydrocarbon Receptor Expression.

J Med Chem 2021 Sep 24;64(17):12964-12977. Epub 2021 Aug 24.

State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, China.

A series of unreported dual-receptor inhibitors targeting both the tubulin colchicine site and AhR were designed and synthesized, and their anti-breast-cancer activities were evaluated. Compound showed the strongest activity with an IC of 0.9 nM in MCF-7 cell lines. Read More

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September 2021

The role of Colchicine on actin polymerization dynamics: as a potent anti-angiogenic factor.

J Biomol Struct Dyn 2021 Aug 23:1-15. Epub 2021 Aug 23.

School of Chemical Sciences, UM-DAE Center for excellence in basic sciences, University of Mumbai, Mumbai, Maharashtra, India.

Over the years, cancer research has focused on different strategies to discover drugs and therapies to treat the metastatic stage of cancer. This stage depends upon the type, and the cause of cancer. One of the central facts about any cancer invasion is the formation of new blood vessels that provide nutrients to these uncontrollably dividing cells. Read More

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Thiophene derivative-loaded nanoparticles mediate anticancer activity through the inhibition of kinases and microtubule assembly.

Adv Ther (Weinh) 2021 Jul 5;4(7). Epub 2021 May 5.

Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242, USA.

Different tetrahydrobenzo[]thiophene derivatives were explored as new tubulin polymerization destabilizers to arrest tumor cell mitosis. A series of compounds incorporating the tetrahydrobenzo[]thiophene scaffold were synthesized, and their biological activities were investigated. The cytotoxicity of each of the synthesized compounds was assessed against a range of cell lines. Read More

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Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as a potential anti-cancer agent.

Bioorg Med Chem Lett 2021 Aug 17:128327. Epub 2021 Aug 17.

Department of Chemistry & Biochemistry, Concordia University, 7141 rue Sherbrooke O., Montréal, QC H4B 1R6, Canada; Department of Biology, Concordia University, 7141 rue Sherbrooke O., Montréal, QC H4B 1R6, Canada.

Several derivatives of a series that share a thienoisoquinoline scaffold have demonstrated potent anti-cancer activity against cancer cell lines A549, HeLa, HCT-116 in the submicromolar concentration range. Structure-activity relationship (SAR) studies on a range of derivatives aided in identifying key pharmacophores in the lead compound. A series of compounds have been identified as the most promising with submicromolar IC values against a lung cancer cell line (A549). Read More

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Colchicine Attenuates Renal Ischemia-Reperfusion-Induced Liver Damage: Implication of TLR4/NF-κB, TGF-β, BAX and Bcl-2 gene expression.

Can J Physiol Pharmacol 2021 Aug 19. Epub 2021 Aug 19.

Menoufia University, 68849, pharmacology and toxicology, Shebin El-Kom, Egypt;

Background: Ischemia/reperfusion injury (IRI) is typically associated with a vigorous inflammatory and oxidative stress response to hypoxia and reperfusion that disturbs the function of the organ. The remote effects of renal IRI on the liver, however, require further study. Renal damage associated with liver disease is a common clinical problem. Read More

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[3 + 2]-Annulation of pyridinium ylides with 1-chloro-2-nitrostyrenes unveils a tubulin polymerization inhibitor.

Org Biomol Chem 2021 Sep 13;19(33):7234-7245. Epub 2021 Aug 13.

Department of Chemistry, North Caucasus Federal University, 1a Pushkin St., Stavropol 355009, Russia.

Indolizines and pyrazolo[1,5-a]pyridines were prepared via [3 + 2]-cycloaddition of pyridinium ylides to 1-chloro-2-nitrostyrenes. The synthesized molecules were evaluated for antiproliferative activities against a BE(2)-C neuroblastoma cell line with several compounds decreasing the viability of cancer cells. Indolizine 9db showed higher potency than that of all-trans-retinoic acid, an approved cancer drug. Read More

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September 2021

Targeted Liposomal Chemotherapies to Treat Triple-Negative Breast Cancer.

Cancers (Basel) 2021 Jul 26;13(15). Epub 2021 Jul 26.

Department of Biomedical Engineering, University of Alabama at Birmingham, 1825 University Blvd, Birmingham, AL 35294, USA.

Triple-negative breast cancers (TNBCs) are highly aggressive and recurrent. Standard cytotoxic chemotherapies are currently the main treatment options, but their clinical efficacies are limited and patients usually suffer from severe side effects. The goal of this study was to develop and evaluate targeted liposomes-delivered combined chemotherapies to treat TNBCs. Read More

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Design, synthesis and bioevaluation of 2,7-diaryl-pyrazolo[1,5-a]pyrimidines as tubulin polymerization inhibitors.

Bioorg Chem 2021 Oct 29;115:105220. Epub 2021 Jul 29.

Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China. Electronic address:

Two series of 2,7-diaryl-pyrazolo[1,5-a]pyrimidines as tubulin polymerization inhibitors were designed to restrict bioactive configuration of (E,Z)-vinylogous CA-4. All of the target compounds were synthesized and then evaluated for their in vitro antiproliferative activities against three cancer cell lines (MCF-7, SGC-7901 and A549). Among them, 6d exhibited the most potent antiproliferative activity against the MCF-7 with IC value of 0. Read More

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October 2021

STING1 is essential for an RNA-virus triggered autophagy.

Autophagy 2021 Aug 2:1-13. Epub 2021 Aug 2.

Department of preventive veterinary medicine, College of Life Science & Technology, Southwest Minzu University, Chengdu, Sichuan, China.

While the functions of STING1 (stimulator of interferon response cGAMP interactor 1) during DNA virus infection had been well documented, the roles STING1 plays during RNA viruses infection is obscure. Infection with foot-and-mouth disease virus (FMDV), a well-known picornavirus, induces endoplasmic reticulum (ER) stress response and autophagy. Here, we found that the FMDV-induced integrated stress response originates from the cellular pattern recognition receptor DDX58/RIG-I (DExD/H-box helicase 58). Read More

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Fluorine Substituted Proline Enhances the Tubulin Binding Potential of a Tetrapeptide at the GTP Binding Pocket Causing the Inhibition of Microtubule Motility and an Antimitotic Effect.

J Phys Chem B 2021 Aug 30;125(31):8768-8780. Epub 2021 Jul 30.

Organic and Medicinal Chemistry and Structural Biology and Bioinformatics Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Jadavpur, Kolkata, West Bengal 700 032, India.

The microtubule is regarded as the key target for designing anticancer and neurotherapeutic drugs due to its functional importance in eukaryotic cells including neurons. The microtubule is a dynamic hollow polymer tube consisting of α,β-tubulin heterodimer. Polymerization of α,β-tubulin heterodimer resulted in microtubule formation. Read More

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TH1902, a new docetaxel-peptide conjugate for the treatment of sortilin-positive triple-negative breast cancer.

Cancer Sci 2021 Jul 27. Epub 2021 Jul 27.

Laboratoire d'Oncologie Moléculaire, Université du Québec à Montréal, Montréal, QC, Canada.

Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of cancers which lacks the expression and/or amplification of targetable biomarkers (ie, estrogen receptor, progestrogen receptor, and human epidermal growth factor receptor 2), and is often associated with the worse disease-specific outcomes than other breast cancer subtypes. Here, we report that high expression of the sortilin (SORT1) receptor correlates with the decreased survival in TNBC patients, and more importantly in those bearing lymph node metastases. By exploiting SORT1 function in ligand internalization, a new anticancer treatment strategy was designed to target SORT1-positive TNBC-derived cells both in vitro and in two in vivo tumor xenografts models. Read More

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In Search of Effective Anticancer Agents-Novel Sugar Esters Based on Polyhydroxyalkanoate Monomers.

Int J Mol Sci 2021 Jul 5;22(13). Epub 2021 Jul 5.

Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Niezapominajek 8, 30-239 Kraków, Poland.

Cancer is one of the deadliest illness globally. Searching for new solutions in cancer treatments is essential because commonly used mixed, targeted and personalized therapies are sometimes not sufficient or are too expensive for common patients. Sugar fatty acid esters (SFAEs) are already well-known as promising candidates for an alternative medical tool. Read More

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Discovery of Novel Diarylamide -Containing Heterocyclic Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity.

Molecules 2021 Jul 2;26(13). Epub 2021 Jul 2.

Key Laboratory of Advanced Drug Preparation Technologies (Ministry of Education), Institute of Drug Discovery & Development, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.

Tubulin has been regarded as an attractive and successful molecular target in cancer therapy and drug discovery. Vicinal diaryl is a simple scaffold found in many colchicine site tubulin inhibitors, which is also an important pharmacophoric point of tubulin binding and anti-cancer activity. As the continuation of our research work on colchicine binding site tubulin inhibitors, we designed and synthesized a series of diarylamide -containing heterocyclic derivatives by the combination of vicinal diaryl core and -containing heterocyclic skeletons into one hybrid though proper linkers. Read More

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Nephrotic-syndrome-associated mutation of KANK2 induces pathologic binding competition with physiological interactor KIF21A.

J Biol Chem 2021 Aug 16;297(2):100958. Epub 2021 Jul 16.

Department of Biology, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China; Academy for Advanced Interdisciplinary Studies, Southern University of Science and Technology, Shenzhen, Guangdong, China; Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, and Shenzhen Key Laboratory of Cell Microenvironment, Department of Biology, Southern Univeristy of Science and Technology, Shenzhen, Guangdong, China. Electronic address:

Nephrotic syndrome (NS) is a common kidney disorder caused by dysfunction of the glomerular filtration barrier. Some genetic mutations identified in NS patients cause amino acid substitutions of kidney ankyrin repeat-containing (KANK) proteins, which are scaffold proteins that regulate actin polymerization, microtubule targeting, and cell adhesion via binding to various molecules, including the kinesin motor protein KIF21A. However, the mechanisms by which these mutations lead to NS are unclear. Read More

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Autophagosome Trafficking.

Adv Exp Med Biol 2021 ;1208:67-77

Department of Physiology and Pathophysiology, Peking University Health Science Center, Beijing, China.

Autophagy is a major intracellular degradation/recycling system that ubiquitously exists in eukaryotic cells. Autophagy contributes to the turnover of cellular components through engulfing portions of the cytoplasm or organelles and delivering them to the lysosomes/vacuole to be degraded. The trafficking of autophagosomes and their fusion with lysosomes are important steps that complete their maturation and degradation. Read More

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Drug-Induced Liver Injury in a Patient with Nonsmall Cell Lung Cancer after the Self-Administration of Fenbendazole Based on Social Media Information.

Case Rep Oncol 2021 May-Aug;14(2):886-891. Epub 2021 Jun 17.

Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya, Japan.

Fenbendazole is a benzimidazole anthelmintic agent, with a broad antiparasitic range in animals such as dogs and pigs. The agent is also reported to exert antitumor effects and inhibit microtubule-associated tubulin polymerization, but its safety and tolerability profile in humans remains unclear. An 80-year-old female patient with advanced nonsmall cell lung cancer (NSCLC) was started on pembrolizumab monotherapy. Read More

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Pyrazoline derivatives as tubulin polymerization inhibitors with one hit for Vascular Endothelial Growth Factor Receptor 2 inhibition.

Bioorg Chem 2021 Sep 1;114:105134. Epub 2021 Jul 1.

School of Chemistry and Chemical Engineering, Nantong University, Nantong, Jiangsu 226019, China. Electronic address:

In this work, to check the effect of the transposition of the rings in typical patterns, a series of pyrazoline derivatives 3a-3t bearing the characteristic 3,4,5-trimethoxy phenyl and thiophene moieties were synthesized and evaluated as tubulin polymerization inhibitors. Basically, as the concise output of our design, a majority of the synthesized compounds showed potency in inhibiting the tubulin polymerization. The top hit, 3q, exhibited potent anti-proliferation activity on cancer cell lines. Read More

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September 2021