ACS Publications. Most Trusted. Most Cited. Most Read
My Activity
CONTENT TYPES

Isolation, Structure, and HIV-1 Integrase Inhibitory Activity of Cytosporic Acid, a Fungal Metabolite Produced by a Cytospora sp.

View Author Information
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, and West Point, Pennsylvania 19486
Cite this: J. Nat. Prod. 2003, 66, 4, 551–553
Publication Date (Web):March 21, 2003
https://doi.org/10.1021/np020533g
Copyright © 2003 American Chemical Society and American Society of Pharmacognosy

    Article Views

    472

    Altmetric

    -

    Citations

    LEARN ABOUT THESE METRICS
    Read OnlinePDF (40 KB)
    Supporting Info (1)»

    Abstract

    HIV-1 integrase is a critical enzyme for replication of HIV, and its inhibition has the potential to lead to an anti-retroviral therapy that has advantages over existing therapies. Cytosporic acid (1) is a polyketide-derived novel natural product that was isolated from a fermentation broth of the filamentous fungus Cytospora sp. collected from Puerto Rico. It inhibited strand transfer reaction of HIV-1 integrase with an IC50 of 20 μM. The isolation, structure elucidation, relative stereochemistry, and activity of 1 are described.

    *

     To whom correspondence should be addressed. Fax:  (732) 594-6880. E-mail:  [email protected].

    Supporting Information Available

    ARTICLE SECTIONS
    Jump To

    A copy of 1H and 13C NMR spectra of 1, Table 1 containing full 1H and 13C NMR assignments including HMBC data, and Figure 1 showing a ChemDraw 3D model and NOESY data. This material is available free of charge via the Internet at http://pubs.acs.org.

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    This article is cited by 25 publications.

    1. Satomi Miura, Kotaro Ishida, Kazuaki Tanaka, Eiji Morita, Masaru Hashimoto. Integrasone Derivatives Isolated from Lepteutypa sp. KT4162 and Their Anti-HIV-1 Integrase Activity. Journal of Natural Products 2023, 86 (4) , 1019-1024. https://doi.org/10.1021/acs.jnatprod.3c00065
    2. Hongxin Liu, Haibo Tan, Yuchan Chen, Xueying Guo, Wenxuan Wang, Heng Guo, Zhaoming Liu, Weimin Zhang. Cytorhizins A–D, Four Highly Structure-Combined Benzophenones from the Endophytic Fungus Cytospora rhizophorae. Organic Letters 2019, 21 (4) , 1063-1067. https://doi.org/10.1021/acs.orglett.8b04107
    3. David R. Williams and J. Cullen Klein . Intramolecular Diels–Alder (IMDA) Studies toward the Synthesis of Australifungin. Stereocontrol in the Acetate Aldol Reaction of β,β′-Branched Aldehydes. Organic Letters 2016, 18 (3) , 420-423. https://doi.org/10.1021/acs.orglett.5b03463
    4. Yan Li, Subin Niu, Bingda Sun, Shuchun Liu, Xingzhong Liu and Yongsheng Che. Cytosporolides A−C, Antimicrobial Meroterpenoids with a Unique Peroxylactone Skeleton from Cytospora sp.. Organic Letters 2010, 12 (14) , 3144-3147. https://doi.org/10.1021/ol101062f
    5. Chinmayee Priyadarsani Mandhata, Chita Ranjan Sahoo, Rabindra Nath Padhy. A comprehensive overview on the role of phytocompounds in human immunodeficiency virus treatment. Journal of Integrative Medicine 2023, 21 (4) , 332-353. https://doi.org/10.1016/j.joim.2023.05.001
    6. Bruce Nzimande, John P. Makhwitine, Nompumelelo P. Mkhwanazi, Sizwe I. Ndlovu. Developments in Exploring Fungal Secondary Metabolites as Antiviral Compounds and Advances in HIV-1 Inhibitor Screening Assays. Viruses 2023, 15 (5) , 1039. https://doi.org/10.3390/v15051039
    7. Boris Yotta Kianfé, Joseph Tchamgoue, Abolfazl Narmani, Rémy Bertrand Teponno, André-Ledoux Njouonkou, Marc Stadler, Simeon Fogue Kouam. Bioactive Secondary Metabolites from Fungi of the Genus Cytospora Ehrenb. (Ascomycota). Molecules 2023, 28 (7) , 3120. https://doi.org/10.3390/molecules28073120
    8. Dinesh Kumar, Pooja Sharma, Shabu, Ramandeep Kaur, Maloba M. M. Lobe, Girish K. Gupta, Fidele Ntie-Kang. In search of therapeutic candidates for HIV/AIDS: rational approaches, design strategies, structure–activity relationship and mechanistic insights. RSC Advances 2021, 11 (29) , 17936-17964. https://doi.org/10.1039/D0RA10655K
    9. Charanjit Kaur, Yachana Mishra, Vijay Mishra, Gaurav K. Saraogi, Murtaza M. Tambuwala. Recent advancement and biomedical applications of fungal metabolites. 2021, 47-67. https://doi.org/10.1016/B978-0-12-821005-5.00004-1
    10. Chayanika Putatunda, Abhishek Walia, Rashmi Sharma, Abhishek Thakur, Rahul Mehta. Fungal metabolites—A potential source of antiviral compounds. 2020, 157-173. https://doi.org/10.1016/B978-0-12-821006-2.00012-1
    11. Zhaoming Liu, Haibo Tan, Kai Chen, Yuchan Chen, Wenge Zhang, Shanchong Chen, Hongxin Liu, Weimin Zhang. Rhizophols A and B, antioxidant and axially chiral benzophenones from the endophytic fungus Cytospora rhizophorae. Organic & Biomolecular Chemistry 2019, 17 (47) , 10009-10012. https://doi.org/10.1039/C9OB02282A
    12. Riikka Linnakoski, Dhanik Reshamwala, Pyry Veteli, Marta Cortina-Escribano, Henri Vanhanen, Varpu Marjomäki. Antiviral Agents From Fungi: Diversity, Mechanisms and Potential Applications. Frontiers in Microbiology 2018, 9 https://doi.org/10.3389/fmicb.2018.02325
    13. Karoon Sadorn, Siriporn Saepua, Nattawut Boonyuen, Tanapong Boonruangprapa, Pranee Rachtawee, Pattama Pittayakhajonwut. Antimicrobial activity and cytotoxicity of xanthoquinodin analogs from the fungus Cytospora eugeniae BCC42696. Phytochemistry 2018, 151 , 99-109. https://doi.org/10.1016/j.phytochem.2018.04.001
    14. Biswajit G Roy. Potential of small-molecule fungal metabolites in antiviral chemotherapy. Antiviral Chemistry and Chemotherapy 2017, 25 (2) , 20-52. https://doi.org/10.1177/2040206617705500
    15. Monika Sharma, Rohit Sharma. Drugs and drug intermediates from fungi: Striving for greener processes. Critical Reviews in Microbiology 2016, 58 , 1-17. https://doi.org/10.3109/1040841X.2014.947240
    16. Azzeme Harun, Sharmili Vidyadaran, Siong Meng Lim, Anthony L J Cole, Kalavathy Ramasamy. Malaysian endophytic fungal extracts-induced anti-inflammation in Lipopolysaccharide-activated BV-2 microglia is associated with attenuation of NO production and, IL-6 and TNF-α expression. BMC Complementary and Alternative Medicine 2015, 15 (1) https://doi.org/10.1186/s12906-015-0685-5
    17. Rohan Pawar, Tiyasa Das, Sanjay Mishra, Nutan, Boskey Pancholi, Satish K. Gupta, Sujata V. Bhat. Synthesis, anti-HIV activity, integrase enzyme inhibition and molecular modeling of catechol, hydroquinone and quinol labdane analogs. Bioorganic & Medicinal Chemistry Letters 2014, 24 (1) , 302-307. https://doi.org/10.1016/j.bmcl.2013.11.014
    18. Gerald F. Bills, Anne W. Dombrowski, Michael A. Goetz. The “FERMEX” Method for Metabolite-Enriched Fungal Extracts. 2012, 79-96. https://doi.org/10.1007/978-1-62703-122-6_5
    19. Azzeme Harun, Richard Muhammad Johari James, Siong Meng Lim, Abu Bakar Abdul Majeed, Anthony LJ Cole, Kalavathy Ramasamy. BACE1 inhibitory activity of fungal endophytic extracts from Malaysian medicinal plants. BMC Complementary and Alternative Medicine 2011, 11 (1) https://doi.org/10.1186/1472-6882-11-79
    20. Sheo B. Singh. Discovery and Development of Natural Product Inhibitors of HIV‐1 Integrase. 2011, 309-323. https://doi.org/10.1002/9781118015377.ch21
    21. Eugene E. Kwan, Shaw G. Huang. Structural Elucidation with NMR Spectroscopy: Practical Strategies for Organic Chemists. European Journal of Organic Chemistry 2008, 2008 (16) , 2671-2688. https://doi.org/10.1002/ejoc.200700966
    22. . Cytotoxic Polyketides from the Marine Sponge Discodermia calyx. Bulletin of the Korean Chemical Society 2007, 990-994. https://doi.org/10.5012/bkcs.2007.28.6.990
    23. Raveendra Dayam, Jinxia Deng, Nouri Neamati. HIV‐1 integrase inhibitors: 2003–2004 update. Medicinal Research Reviews 2006, 26 (3) , 271-309. https://doi.org/10.1002/med.20054
    24. Kithsiri B. Herath, Hiranthi Jayasuriya, Gerald F. Bills, Jon D. Polishook, Anne W. Dombrowski, Ziqiang Guan, Peter J. Felock, Daria J. Hazuda, Sheo B. Singh. Isolation, Structure, Absolute Stereochemistry, and HIV-1 Integrase Inhibitory Activity of Integrasone, a Novel Fungal Polyketide. Journal of Natural Products 2004, 67 (5) , 872-874. https://doi.org/10.1021/np0340504
    25. Hideaki Oikawa, Tetsuo Tokiwano. Enzymatic catalysis of the Diels–Alder reaction in the biosynthesis of natural products. Nat. Prod. Rep. 2004, 21 (3) , 321-352. https://doi.org/10.1039/B305068H

    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