ArticleJournal of medicinal chemistry2014
Optimization of 4-(N-cycloamino)phenylquinazolines as a novel class of tubulin-polymerization inhibitors targeting the colchicine site.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 70 citations in OpenAlex.
- Recent Advancements in the Development of HDAC/Tubulin Dual-Targeting Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Design and synthesis of N-aryl-2-trifluoromethyl-quinazoline-4-amine derivatives as potential Werner-dependent antiproliferative agents.Molecular diversity · 2025Article
- Synthesis of Functionalized Benzocycloheptene Analogs.Essential chem · 2025Article
- Verubulin (Azixa) Analogues with Increased Saturation: Synthesis, SAR and Encapsulation in Biocompatible Nanocontainers Based on CaPharmaceuticals (Basel, Switzerland) · 2023Article
- Design, Synthesis, and Biological Evaluation of Pyrimidine Dihydroquinoxalinone Derivatives as Tubulin Colchicine Site-Binding Agents That Displayed Potent Anticancer Activity Both In Vitro and In Vivo.ACS pharmacology & translational science · 2023Article
- Molecular interactions at the colchicine binding site in tubulin: An X-ray crystallography perspective.Drug discovery today · 2022Review
- X-ray Crystallography-Guided Design, Antitumor Efficacy, and QSAR Analysis of Metabolically Stable Cyclopenta-Pyrimidinyl Dihydroquinoxalinone as a Potent Tubulin Polymerization Inhibitor.Journal of medicinal chemistry · 2021Article
- Discovery of Novel DiarylamideMolecules (Basel, Switzerland) · 2021Article
- Discovery of a Potent Anticancer Agent PVHD303 withACS medicinal chemistry letters · 2020Article
- Kalshiolin A, new lignan fromJournal of Asian natural products research · 2020Article
- Scaffold Hopping-Driven Optimization of 4-(Quinazolin-4-yl)-3,4-dihydroquinoxalin-2(1ACS medicinal chemistry letters · 2020Article
- Current advances of tubulin inhibitors as dual acting small molecules for cancer therapy.Medicinal research reviews · 2019Review
- Salvisertin A, a New Hexacyclic Triterpenoid, and Other Bioactive Terpenes from Salvia deserta Root.Chemistry & biodiversity · 2018Article
- Heterocyclic-Fused Pyrimidines as Novel Tubulin Polymerization Inhibitors Targeting the Colchicine Binding Site: Structural Basis and Antitumor Efficacy.Journal of medicinal chemistry · 2018Article
- Article
- In Vivo and Mechanistic Studies on Antitumor Lead 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin-2(1H)-one and Its Modification as a Novel Class of Tubulin-Binding Tumor-Vascular Disrupting Agents.Journal of medicinal chemistry · 2017Article
- An insight into the therapeutic potential of quinazoline derivatives as anticancer agents.MedChemComm · 2017Review
- Current Advances of Tubulin Inhibitors in Nanoparticle Drug Delivery and Vascular Disruption/Angiogenesis.Molecules (Basel, Switzerland) · 2016Review
- Synthesis, biological evaluation, and physicochemical property assessment of 4-substituted 2-phenylaminoquinazolines as Mer tyrosine kinase inhibitors.Bioorganic & medicinal chemistry · 2016Article
- Optimization of N-aryl-6-methoxy-1,2,3,4-tetrahydroquinolines as tubulin polymerization inhibitors.Bioorganic & medicinal chemistry · 2015Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 3 countries.
Funding
Abstract
The 6-methoxy-1,2,3,4-tetrahydroquinoline moiety in prior leads 2-chloro- and 2-methyl-4-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)quinazoline (1a and 1b) was modified to produce 4-(N-cycloamino)quinazolines (4a-c and 5a-m). The new compounds were evaluated in cytotoxicity and tubulin inhibition assays, resulting in the discovery of new tubulin-polymerization inhibitors. 7-Methoxy-4-(2-methylquinazolin-4-yl)-3,4-dihydroquinoxalin- 2(1H)-one (5f), the most potent compound, exhibited high in vitro cytotoxic activity (GI50 1.9-3.2 nM), significant potency against tubulin assembly (IC50 0.77 μM), and substantial inhibition of colchicine binding (99% at 5 μM). In mechanism studies, 5f caused cell arrest in G2/M phase, disrupted microtubule formation, and competed mostly at the colchicine site on tubulin. Compound 5f and N-methylated analogue 5g were evaluated in nude mouse MCF7 xenograft models to validate their antitumor activity. Compound 5g displayed significant in vivo activity (tumor inhibitory rate 51%) at a dose of 4 mg/kg without obvious toxicity, whereas 5f unexpectedly resulted in toxicity and death at the same dose.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.