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Synthesis and Biological Evaluation of Tricyclic Guanidine Analogues of Batzelladine K for Antimalarial, Antileishmanial, Antibacterial, Antifungal, and Anti-HIV Activities

Authors

  • Nafees Ahmed,

    1. Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
    2. Jeffrey Cheah School of Medicine and Health Sciences, MONASH University Sunway Campus, Bandar Sunway, Selangor Darul Ehsan 46150, Malaysia
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  • Keyur G. Brahmbhatt,

    1. Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
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  • Shabana I. Khan,

    1. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
    2. Department of Pharmacognosy, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
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  • Melissa Jacob,

    1. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
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  • Babu L. Tekwani,

    1. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
    2. Department of Pharmacology, School of Pharmacy, University of Mississippi, MS 38677, USA
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  • Sudeep Sabde,

    1. National Center for Cell Science (NCCS), Pune University Campus, Ganeshkhind, Pune, Maharashtra 411007, India
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  • Debashis Mitra,

    1. National Center for Cell Science (NCCS), Pune University Campus, Ganeshkhind, Pune, Maharashtra 411007, India
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  • Inder P. Singh,

    1. Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
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  • Ikhlas A. Khan,

    1. National Center for Natural Products Research, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
    2. Department of Pharmacognosy, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA
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  • Kamlesh K. Bhutani

    Corresponding author
    1. Department of Natural Products, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab 160062, India
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Corresponding author: Kamlesh K. Bhutani, kkbhutani@niper.ac.in

Abstract

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV-1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine-sensitive D6 strain with IC50 1.25 and 0.88 μm and chloroquine-resistant W2 strain with IC50 1.64 and 1.07 μm, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC50 2.39 and 2.78 μm and IC90 11.27 and 12.76 μm, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC50 < 3.02 μm and MIC/MBC/MFC <6 μm. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV-1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.

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