Publications by authors named "Madhuri T Patil"

Article Synopsis
  • Toll-like receptors (TLRs) are crucial for linking the innate and adaptive immune systems, with TLR2 agonists like PamCSK showing potential as vaccine adjuvants, but facing issues like poor water solubility and complicated synthesis.
  • The new compound PamCS-DMAPA (13) was developed to be water-soluble and effectively enhance the immune response to SARS-CoV2 and hepatitis B vaccines in mice, outperforming earlier options in manufacturability.
  • Combining PamCS-DMAPA with 2% aluminum hydroxide gel significantly boosted vaccine effectiveness, marking it as a promising TLR2-targeted adjuvant for future development.
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TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation.

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The Groebke-Blackburn-Bienaymé (GBB) reaction is a well-established three-component reaction for synthesizing imidazofused scaffolds from heterocyclic amidines, aldehydes, and isonitriles. However, the replacement of pyridoxal as an aldehyde component in this reaction results in the formation of the furo[2,3-]pyridine skeleton as an "unusual GBB product". Despite the interesting nature of this unusual reaction, not much work was further reported.

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Toll-like receptor (TLR)-7 agonists are immunostimulatory vaccine adjuvants. A systematic structure-activity relationship (SAR) study of TLR7-active 1-benzyl-2-butyl-1-imidazo[4,5-]quinolin-4-amine led to the identification of a potent hTLR7-specific -hydroxymethyl IMDQ with an EC value of 0.22 μM.

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Nucleotide-binding oligomerization domain 2 (NOD2) is a receptor of the innate immune system that is capable of perceiving bacterial and viral infections. Muramyl dipeptide (MDP, N-acetyl muramyl L-alanyl-d-isoglutamine), identified as the minimal immunologically active component of bacterial cell wall peptidoglycan (PGN) is recognized by NOD2. In terms of biological activities, MDP demonstrated vaccine adjuvant activity and stimulated non-specific protection against bacterial, viral, and parasitic infections and cancer.

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Article Synopsis
  • * Researchers have created a library of imidazo-fused heterocycles and found that imidazo-pyrimidine is particularly effective against leishmanial forms, showing an IC value of 6.63 μM, which is about twice as potent as the standard drug miltefosine.
  • * The imidazo-pyrimidine compound demonstrates strong selective activity against the parasites while being over 10 times more harmful to the parasites compared to human cells, suggesting it could be a promising candidate for new leishman
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Indoleamine-2,3-dioxygenase 1 (IDO1) is an immunomodulatory enzyme known to catalyse the initial and rate limiting step of kynurenine pathway of l-tryptophan metabolism. IDO1 enzyme over expression plays a crucial role in progression of cancer, malaria, multiple sclerosis and other life-threatening diseases. Several efforts over the last two decades have been invested by the researchers for the discovery of different IDO1 inhibitors and the plasticity of the IDO1 enzyme ligand binding pocket provide ample opportunities to develop new heterocyclic scaffolds targeting this enzyme.

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Better adjuvants are needed for vaccines against seasonal influenza. TLR7 agonists are potent activators of innate immune responses and thereby may be promising adjuvants. Among the imidazoquinoline compounds, 1-benzyl-2-butyl-1H-imidazo[4,5-c]quinolin-4-amine (BBIQ) was reported to be a highly active TLR7 agonist but has remained relatively unexplored because of its commercial unavailability.

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Diacylated PAMCSK, a highly expensive lipopeptide with desirable aqueous solubility and a broad spectrum of cytokine/chemokine induction is a most potent dual (human and murine) Toll-Like Receptor-2 (TLR2) agonist. Besides such thrilling characteristics, its synthetic process is not reported in the literature. The present report describes an efficient and scalable 20 step synthesis of PAMCSK in good yield (all steps > 60%) along with a clear description of the hindrances and easy solutions adopted in each step.

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The conversion of myo-inositol to epi-inositol can be achieved by the hydride reduction of an intermediate epi-inosose derived from myo-inositol. (-)-epi-Inosose, (I), crystallized in the monoclinic space group P2(1), with two independent molecules in the asymmetric unit [Hosomi et al. (2000).

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