Immunomodulation and Development of Immunotherapies for Human Autoimmunity, Inflammation, Infection, Allergy, and Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 1370

Special Issue Editors


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Guest Editor
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, USA
Interests: immunology; immunology in type 1 diabetes; host-parasite interaction; immunomodulation by parasite; autoimmunity and inflammation; T cell biology
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Co-Guest Editor
Albert Einstein College of Medicine of Yeshiva University, New York, NY, USA
Interests: extracellular vesicles

Special Issue Information

Dear Colleagues,

In mammals, the immune system protects the host by responding to attacks from a broad range of pathogens such as bacteria, parasites, and viruses while avoiding misguided or irrational immune reactions that are deleterious to the host. Both protective and detrimental immune responses are primarily facilitated by T and B cells, which possess enormous diversity in antigen recognition, high antigen specificity, potent effector activity, and long-lasting immunologic memory. Because of this potency, serious damage to the host may ensue if aberrant immune responses, such as autoimmunity or allergy, are triggered. A major challenge in immunology and biomedicine is to determine how the unresponsiveness of the adaptive immune system to self-antigens is established and maintained, and how the quality and magnitude of adaptive immune responses to non-self-antigens are controlled to avoid damage to the host. Despite technological advances, treatments for many and inflammatory and autoimmune diseases, including type 1 diabetes and rheumatoid arthritis, primarily rely on broad-spectrum immunosuppressive agents. However, the associated immunosuppressive regimens result in severe side effects, and safer and more effective treatments are thus required. Hence, increasing efforts have focused on developing immunotherapies aimed at targeting the underlying disease process to modulate the immune system, maximize critical cell function, and induce and/or enhance T-reg cells and their function.

Dr. Nitin P. Amdare
Dr. Phaneendra K. Duddempudi
Guest Editors

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Keywords

  • immunomodulation
  • immunotherapies
  • immune system
  • human autoimmunity
  • inflammation
  • infection
  • allergy
  • cancer

Published Papers (1 paper)

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Research

17 pages, 7298 KiB  
Article
Michael Adduct of Sulfonamide Chalcone Targets Folate Metabolism in Brugia Malayi Parasite
by Priyanka S. Bhoj, Sandeep P. Bahekar, Shambhavi Chowdhary, Namdev S. Togre, Nitin P. Amdare, Lingaraj Jena, Kalyan Goswami and Hemant Chandak
Biomedicines 2023, 11(3), 723; https://doi.org/10.3390/biomedicines11030723 - 27 Feb 2023
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Abstract
A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by [...] Read more.
A series of Michael adducts of malononitrile and sulfonamide chalcones were synthesized, characterized, and evaluated for their antifilarial activity. Out of 14 compounds, N-(4-(4,4-dicyano-3-p-tolylbutanoyl)phenyl)benzenesulfonamide showed favorable drug-likeness properties with marked antifilarial effects at micro-molar dosages. Apoptosis in Brugia malayi microfilariae was confirmed by EB/AO staining, MTT assay, and cytoplasmic cytochrome c ELISA. Since chalcone and folate synthesis pathways share the same substrate, we hypothesize a structural analogy-based inhibition of folate metabolism by this compound. Molecular docking against a pre-validated BmDHFR protein showed more favorable thermodynamic parameters than a positive control, epicatechin-3-gallate. The compound significantly suppressed the DHFR activity in a parasite extract in vitro. Our hypothesis is also supported by a significant reversal of DHFR inhibition by folate addition, which indicated a plausible mechanism of competitive inhibition. These results demonstrate that targeting filarial folate metabolism through DHFR with consequent apoptosis induction might be rewarding for therapeutic intervention. This study reveals a novel rationale of the structural analogy-based competitive inhibition of DHFR by Michael adducts of sulfonamide chalcones. Full article
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