Abstract
The binding mode analysis of Gefitinib revealed that 6-propylmorpholino group (sidechain) shows no interactions due to its weak electron density. In order to modify the electron density of Gefitinib’s sidechain, novel pyrrolidino analogs of Gefitinib where morpholino groups were replaced by substituted pyrrolidino groups were synthesized. Gefitinib derivatives with high electronegativity atoms or groups in the pyrrolidino moiety always exhibit high potent activity against EGFR and human cancer cell lines, A431, MDA-MB-231 and A549. Among these derivatives, 16 displayed the best pharmacokinetic properties that make it to be a promising candidate for developing drugs to replace Gefitinib.
Keywords: Gefitinib, anticancer, EGFR, pyrrolidino analogue, pharmacokinetic property.
Anti-Cancer Agents in Medicinal Chemistry
Title:Pyrrolidino Analogues of Gefitinib with Improved EGFR Inhibition, Cancer Cell Cytotoxicity, and Pharmacokinetic Properties
Volume: 16 Issue: 12
Author(s): Jing-Kun Fang, Zhimin Xu, Yingjun Zhang, Weihong Zhang, Bing Liu, Yu Fang and Tengxiao Sun
Affiliation:
Keywords: Gefitinib, anticancer, EGFR, pyrrolidino analogue, pharmacokinetic property.
Abstract: The binding mode analysis of Gefitinib revealed that 6-propylmorpholino group (sidechain) shows no interactions due to its weak electron density. In order to modify the electron density of Gefitinib’s sidechain, novel pyrrolidino analogs of Gefitinib where morpholino groups were replaced by substituted pyrrolidino groups were synthesized. Gefitinib derivatives with high electronegativity atoms or groups in the pyrrolidino moiety always exhibit high potent activity against EGFR and human cancer cell lines, A431, MDA-MB-231 and A549. Among these derivatives, 16 displayed the best pharmacokinetic properties that make it to be a promising candidate for developing drugs to replace Gefitinib.
Export Options
About this article
Cite this article as:
Fang Jing-Kun, Xu Zhimin, Zhang Yingjun, Zhang Weihong, Liu Bing, Fang Yu and Sun Tengxiao, Pyrrolidino Analogues of Gefitinib with Improved EGFR Inhibition, Cancer Cell Cytotoxicity, and Pharmacokinetic Properties, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (12) . https://dx.doi.org/10.2174/1871520616666160622094153
DOI https://dx.doi.org/10.2174/1871520616666160622094153 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Ginsenoside Rh2 Inhibits Migration of Lung Cancer Cells under Hypoxia via mir-491
Anti-Cancer Agents in Medicinal Chemistry Subject Index to Volume 1
Medicinal Chemistry Reviews - Online (Discontinued) Design, Synthesis and Evaluation of Novel 3/4-((Substituted benzamidophenoxy) methyl)-N-hydroxybenzamides/propenamides as Histone Deacetylase Inhibitors and Antitumor Agents
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Potential of Targeting Glypican-3 in Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer
Current Pharmaceutical Design Cytotoxic Nitrobenzoyloxy-substituted Sesquiterpenes from Spongederived Endozoic Fungus Aspergillus insulicola MD10-2
Current Pharmaceutical Biotechnology Drug Combinations Enhancing the Antineoplastic Effects of Erlotinib in High-Grade Glioma
Recent Patents on Anti-Cancer Drug Discovery Sorafenib (BAY 43-9006) in Hepatocellular Carcinoma Patients: From Discovery to Clinical Development
Current Medicinal Chemistry Network of WNT and Other Regulatory Signaling Cascades in Pluripotent Stem Cells and Cancer Stem Cells
Current Pharmaceutical Biotechnology Recent Progress on the Mangrove Plants: Chemistry and Bioactivity
Current Organic Chemistry Nanoparticle-Based Tumor Theranostics with Molecular Imaging
Current Pharmaceutical Biotechnology Association of EGF rs4444903 and XPD rs13181 Polymorphisms with Cutaneous Melanoma in Caucasians
Medicinal Chemistry Fluoroquinolones Prophylaxis of Bacterial Infections in Neutropenic Patients: Time to Re-Evaluate
Current Cancer Therapy Reviews Power from the Garden: Plant Compounds as Inhibitors of the Hallmarks of Cancer
Current Medicinal Chemistry The Role of Bax/Bcl-2 and Pro-Caspase Peptides in Hypoxia/Reperfusion-Dependent Regulation of MAPKERK: Discordant Proteomic Effect of MAPKp38
Protein & Peptide Letters Synthesis of Some Benzothiazole Based Piperazine-Dithiocarbamate Derivatives and Evaluation of Their Anticancer Activities
Letters in Drug Design & Discovery Molecular Bases of Liver Cancer Refractoriness to Pharmacological Treatment
Current Medicinal Chemistry Synthesis, Computational Study, and Evaluation of In Vitro Antimicrobial, Antibiofilm, and Anticancer Activities of New Sulfanyl Aminonaphthoquinone Derivatives
Letters in Drug Design & Discovery ent-Kaurane Diterpenoids from Croton tonkinensis Induce Apoptosis in Colorectal Cancer Cells through the Phosphorylation of JNK Mediated by Reactive Oxygen Species and Dual-Specificity JNK Kinase MKK4
Anti-Cancer Agents in Medicinal Chemistry The Significance of Ubiquitin Proteasome Pathway in Cancer Development
Recent Patents on Anti-Cancer Drug Discovery