- Synthesis of quinoline based molecular probes for detection of nitric oxide
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Nitric oxide (NO), an important signaling molecule of the immune, vascular and nervous system was found to be present in different concentrations in biological fluids such as blood and plasma as well as in neural tissue and endothelium. A variety of competent probes may be required to detect NO and understand its complicated biochemistry, and establish the correlation of its concentrations among different biological media to its biological effect. In order to find new probes as NO sensors, four quinoline-derived ortho-diamines were synthesized and their structures and purities were confirmed by various spectroscopic methods including single-crystal X-ray diffraction. The molecules were investigated for the bimodal sensing (UV–visible and fluorescence) potential for NO. All the probes have showcased both UV–visible and fluorescent signals towards the presence of NO due to the formation of corresponding triazoles. Interestingly, the limit of detection was observed in the nanomolar range (56.1–95 nM) for the four ligands using colorimetric signals. Among the prepared molecules, the N4-(4-chlorobenzyl)quinoline-3,4-diamine exhibited superior sensing parameters viz the limit of detection (LOD), formation constant (Kf), and quenching constant (Ksv). An isolated triazole further confirmed the proposed mechanism of NO detection.
- Kansal, Sushil K.,Kaur, Manpreet,Kaushik, Deepender,Mehta, Surinder K.,Mutreja, Vishal,Pathania, Khushboo,Pawar, Sandip V.,Sahoo, Subash Chandra,Saini, Vaneet,Salunke, Deepak B.
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- Toll-like receptor-7/8 agonist kill Leishmania amazonensis by acting as pro-oxidant and pro-inflammatory agent
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Objectives: Evaluation of the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists. Methods: TLR7/8-active imidazoquinolines (2 and 3) were synthesized and assessed for activity against Leishmania amazonensis-intracellular amastigotes using mouse peritoneal macrophages. The production of reactive oxygen species (ROS), nitric oxide (NO) and cytokines was determined in infected and non-infected macrophages. Key findings: The imidazoquinolines, 2 and 3, were primarily agonists of TLR7 with compound 3 also showing modest TLR8 activity. Docking studies showed them to occupy the same binding pocket on TLR7 and 8 as the known agonists, imiquimod and resiquimod. Compounds 2 and 3 inhibited the growth of L. amazonensis-intracellular amastigotes with the most potent compound (3, IC50 = 5.93 μM) having an IC50 value close to miltefosine (IC50 = 4.05 μM), a known anti-Leishmanial drug. Compound 3 induced macrophages to produce ROS, NO and inflammatory cytokines that likely explain the anti-Leishmanial effects. Conclusions: This study shows that activating TLR7 using compounds 2 or 3 induces anti-Leishmanial activity associated with induction of free radicals and inflammatory cytokines able to kill the parasites. While 2 and 3 had a very narrow cytotoxicity window for macrophages, this identifies the possibility to further develop this chemical scaffold to less cytotoxic TLR7/8 agonist for potential use as anti-Leishmanial drug.
- Coimbra, Elaine S,Da Silva, Adilson D,Dib, Paula R. B,Fung, Johnson,Granato, Juliana T,Kaushik, Deepender,Macedo, Gilson C,Petrovsky, Nikolai,Piplani, Sakshi,Salunke, Deepak B.
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p. 1180 - 1190
(2022/03/31)
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- High Turnover Pd/C Catalyst for Nitro Group Reductions in Water. One-Pot Sequences and Syntheses of Pharmaceutical Intermediates
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Commercially available Pd/C can be used as a catalyst for nitro group reductions with only 0.4 mol % Pd loading. The reaction can be performed using either silane as a transfer hydrogenating agent or simply a hydrogen balloon (μ1 atm pressure). With this technology, a series of nitro compounds was reduced to the desired amines in high chemical yields. Both the catalyst and surfactant were recycled several times without loss of reactivity.
- Gallou, Fabrice,Li, Xiaohan,Lipshutz, Bruce H.,Takale, Balaram S.,Thakore, Ruchita R.
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supporting information
p. 8114 - 8118
(2021/10/25)
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- Design, synthesis, and biological activity of TLR7-based compounds for chemotherapy-induced alopecia
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Hair loss is a common dermatosis symptom and side-effect in cancer chemotherapeutics. Imiquimod application at mid and late telogen activated the hair follicle stem cells leading to premature hair cycle entry. Based on quinoline structure, a newly synthesized compound 6b displayed proliferation activity in vitro and in vivo through branch chain replacement and triazole ring cyclization. Toll-like receptors (TLRs) are also critical mediators of the immune system, and their activation is linked to various diseases. The present study aimed to expand new agonists within co-crystallization of TLR7 (PDB code: 5GMH); however, biological assays of NF-κB activity and NO-inhibition indicated that five selected compounds were TLR7 antagonists. Molecular docking indicated the binding mode differences: antagonists binding TLR7 in a different direction and interacting with adjacent TLR7 with difficulty in forming dimers.
- Yang, Jincheng,Chen, Kun,Wang, Bin,Wang, Liudi,Qi, Shuya,Wang, Weihua
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- AMINE COMPOUNDS HAVING ANTI-INFLAMMATORY, ANTIFUNGAL, ANTIPARASITIC AND ANTICANCER ACTIVITY
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Amine compounds having activity against inflammation, fungi, unicellular parasitic microorganisms, and cancer are described. The compounds contain a monocyclic, bicyclic, or tricyclic aromatic ring having one, two, or three ring nitrogen atoms.
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Page/Page column 174
(2014/08/19)
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- Synthesis and structure - Activity-relationships of 1H-imidazo[4,5-c] quinolines that induce interferon production
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1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.
- Gerster, John F.,Lindstrom, Kyle J.,Miller, Richard L.,Tomai, Mark A.,Birmachu, Woubalem,Bomersine, Shannon N.,Gibson, Shiela J.,Imbertson, Linda M.,Jacobson, Joel R.,Knafla, Roy T.,Maye, Peter V.,Nikolaides, Nickolas,Oneyemi, Folakemi Y.,Parkhurst, Gwen J.,Pecore, Sharon E.,Reiter, Michael J.,Scribner, Lisa S.,Testerman, Tracy L.,Thompson, Natalie J.,Wagner, Tammy L.,Weeks, Charles E.,Andre, Jean-Denis,Lagain, Daniel,Bastard, Yvon,Lupu, Michel
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p. 3481 - 3491
(2007/10/03)
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- PREPARATION OF 1H-IMIDAZO [4,5-C] QUINOLIN-4-AMINES VIA NOVEL 1H-IMIDAZO [4,5-C] QUINOLIN-4-CYANO AND 1H-IMIDAZO [4,5-C] QUINOLIN-4-CARBOXAMIDE INTERMEDIATES
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The invention relates to a process for the synthesis of 1H-imidazo[4,5-c] quinoline 4-cyano and 1H-imidazo[4,5-c] quinoline 4- carboxamide intermediates useful in preparing 1H-imidazo[4,5-C] quinoline 4-amines, a process for preparing 1H-imidazo [4,5-C] quinoline 4-amines using such intermediates; and, to the 1H-imidazo[4,5-c] quinoline 4-cyano and 1H-imidazo[4,5-c] quinoline 4- carboxamide intermediates. More particularly, the invention relates to a process for the preparation of 1-isobutyl-1H-imidazo [4,5-C] quinoline 4-amine (Imiquimod) using two intermediates, 1-isobutyl-1H-imidazo[4,5-c]quinoline 4-cyano and 1-isobutyl-1H-imidazo[4,5-c]quinoline 4-carboxamide, and to the said intermediates.
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- 1H-IMIDAZO[4,5-C]QUINOLIN-4-AMINES AND ANTIVIRAL USE
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1H-Imidazo[4,5-c]quinolin-4-amines which are antivirals. Pharmacological methods of using such compounds and pharmaceutical compositions containing such compounds are also described
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- 1H-imidazo[4,5-c]quinolines and their use as bronchodilating agents
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1H-imidazo[4,5-c]quinoline which are bronchodilators. Pharmacological methods of using the compounds as bronchodilators, pharmaceutical compositions containing the compounds, and synthetic intermediate for preparing the compounds are also described.
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