Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
Exploration and Biological Evaluation of 1,3-Diamino-7H-pyrrol[3,2-f]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:J. Med. Chem. 2023, 66, 20, 13946-13967
    Article

    Exploration and Biological Evaluation of 1,3-Diamino-7H-pyrrol[3,2-f]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors
    Click to copy article linkArticle link copied!

    • Zihao Zhu
      Zihao Zhu
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Zihao Zhu
    • Cantong Chen
      Cantong Chen
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Cantong Chen
    • Jie Zhang
      Jie Zhang
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Jie Zhang
    • Fangfang Lai*
      Fangfang Lai
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      *Email: [email protected]
      More by Fangfang Lai
    • Jing Feng
      Jing Feng
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Jing Feng
    • Guangxu Wu
      Guangxu Wu
      Department of Pharmacy, The People Hospital of Liupanshui City, Guizhou, Liupanshui 553000, China
      More by Guangxu Wu
    • Jie Xia
      Jie Xia
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Jie Xia
      Orcidhttps://orcid.org/0000-0002-9567-3763
    • Wenxuan Zhang
      Wenxuan Zhang
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Wenxuan Zhang
      Orcidhttps://orcid.org/0000-0002-2046-3366
    • Zunsheng Han
      Zunsheng Han
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Zunsheng Han
    • Chi Zhang
      Chi Zhang
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Chi Zhang
    • Qingyun Yang
      Qingyun Yang
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Qingyun Yang
    • Yuchen Wang
      Yuchen Wang
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Yuchen Wang
    • Bo Liu
      Bo Liu
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      More by Bo Liu
    • Tianlei Li*
      Tianlei Li
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      *Email: [email protected]
      More by Tianlei Li
      Orcidhttps://orcid.org/0000-0001-5613-8154
    • Song Wu*
      Song Wu
      State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
      *Email: [email protected]
      More by Song Wu
    Other Access OptionsSupporting Information (4)

    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2023, 66, 20, 13946–13967
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.3c00891
    Published September 12, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7H-pyrrol[3,2-f]quinazoline derivative (PQD) structure bearing condensed rings. Compound 6r exhibited therapeutic effects on mouse models of systemic infection and thigh infection caused by methicillin-resistant Staphylococcus aureus (MRSA) ATCC 43300. Moreover, methyl-modified PQD compound 8a showed a strong efficacy in a murine model of breast cancer, which was better than the effects of taxol. The findings showcased in this study highlight the promising capabilities of novel DHFR inhibitors in addressing bacterial infections as well as breast cancer.

    Copyright © 2023 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c00891.

    • Metabolic stability; 1H NMR; 13C NMR; HPLC traces and HRMS (PDF)

    • Molecular formula strings (CSV)

    • Docking pose of compound 6r and IRS-16 to ecDHFR (PDB)

    • Docking pose of compounds 6p and 8a to hDHFR (PDB)

    Terms & Conditions

    Electronic Supporting Information files are available without a subscription to ACS Web Editions. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information. Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting Information from the ACS website, either in whole or in part, in either machine-readable form or any other form without permission from the American Chemical Society. For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. Information about how to use the RightsLink permission system can be found at http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 1 publications.

    1. Zongkai Huang, Xupeng Gou, Xudong Hang, Ting Shi, Jiaxing Yang, Yan Liu, Xinlian He, Jin Li, Keao Quan, Hongkai Bi, Youfu Luo. Design, Synthesis, and Biological Evaluation of 5-(5-Iodo-2-isopropyl-4-methoxyphenoxy)pyrimidine-2,4-diamine (AF-353) Derivatives as Novel DHFR Inhibitors against Staphylococcus aureus. Journal of Medicinal Chemistry 2024, 67 (6) , 4757-4781. https://doi.org/10.1021/acs.jmedchem.3c02355
    Download PDF
    Go to Journal of Medicinal Chemistry
    Get e-Alerts
    Get e-Alerts

    Journal of Medicinal Chemistry

    Cite this: J. Med. Chem. 2023, 66, 20, 13946–13967
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jmedchem.3c00891
    Published September 12, 2023
    Copyright © 2023 American Chemical Society
    Request reuse permissions

    Article Views

    2520

    Altmetric

    -

    Citations

    1
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.