The arylsulfonamides were synthesized from aryl sulfonyl chloride and aromatic amines in dichloromethane in the presence of pyridine. The aryne chemistry was used to prepare diarylsulfonamide from ...arylsulfonamides and O‐silylaryl triflate with CsF in acetonitrile at room temperature for 30 min. The synthesized compounds were evaluated for cytotoxicity followed by the cytokine/inflammatory marker's inhibition capability and its mechanism of action in RAW‐264.7 cells. Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions and inflammation‐associated disorders. Hence, reducing the IL‐6 levels in inflammatory conditions can serve as an attractive therapeutic target in dealing the inflammation. Among 42 compounds, seven compounds showed significant inhibition of IL‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells at 12.5 μM concentration. Further, investigation revealed that the IC50 value of these compounds for reducing IL‐6 levels was found to be in the range of 2.6 to 9.7 μM. The promising compounds 5y (IC50 of 2.6 μM) and 5n (IC50 of 4.1 μM) along with other derivatives fulfil drug‐likeness parameters laid down by Lipinski's rule of five. Further, RT‐qPCR and Western‐blot analysis revealed that treatment with 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker's expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic evaluation showed that 5n exhibited anti‐inflammatory properties by modulating the nuclear factor‐κB (NF‐κB) activation. The identified compound can be a promising candidate for further discovery efforts to generate a preclinical candidate effective in inflammation.
Elevated interleukin‐6 (IL‐6) levels have been reported in inflammatory conditions. N,N‐Diarylsulfonamide reduces proinflammatory cytokine interleukin‐6 levels in lipopolysaccharide (LPS) challenged RAW‐264.7 cells. Analysis using RT‐qPCR and Western‐blot analysis revealed that treatment with promising compound 5n significantly reduced the expression of pro‐inflammatory, inflammatory and macrophage marker's expression (IL‐1β, CCL2, COX2 and CD68) compared to LPS control. The mechanistic insights reveal that 5n exhibits anti‐inflammatory activity by modulating the nuclear factor‐κB (NF‐κB) activation.
Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3‐aryl‐substituted imidazo1,2‐apyridines as potent antituberculosis agents. A small library of 3‐aryl‐substituted ...imidazo1,2‐apyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd‐catalyzed C−N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key π–π interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB.
A small library of 3‐aryl‐substituted imidazo1,2‐apyridines was synthesized using direct arylation, followed by nitro reduction and Pd‐catalyzed C–N coupling reactions. The obtained compounds were evaluated against Mycobacterium tuberculosis H37Rv, identifying compound 26 as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv and a selectivity index of 35.
A facile strategy was developed for the synthesis of biologically important 4,5‐dihydropyrrolo1,2‐aquinoxalines and pyrrolo1,2‐aquinoxalin‐2‐ones by treating 2‐(1H‐pyrrol‐1‐yl)anilines with ...imidazo1,2‐apyridine‐3‐carbaldehyde or isatin, using amidosulfonic acid (NH3SO3) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d, 3g, 5d, 5e, and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF‐7, and B16‐F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b, 5e, 5d, 5g, and 5l at 32 µg/ml.
A facile strategy was developed for the synthesis of biologically important 4,5‐dihydropyrrolo1,2‐aquinoxalines and pyrrolo1,2‐aquinoxalin‐2‐ones, which were then evaluated for their antituberculosis, antibacterial, and anticancer activities. Compounds 3d and 3e demonstrated good activity against Mycobacterium tuberculosis H37Rv, whereas compounds 3d, 3g, 5d, 5e, and 5i showed remarkable inhibition of A549, DU145, HeLa, HepG2, MCF‐7, and B16‐F10 cells. Staphylococcus aureus was inhibited by compounds 5b, 5e, 5d, 5g, and 5l.
A facile ligand-free method for Pd(OAc) 2 catalysed decarboxylative arylation of imidazo1,2- a pyridine-3-carboxylic acids with hetero(aryl) bromides has been developed. This method is applicable to ...a variety of (hetero)aryl bromides as coupling partners. Electron withdrawing and donating groups on imidazo1,2- a pyridine-3-carboxylic acids are well tolerated. It represents the first general protocol for ligand-free Pd(OAc) 2 catalysed decarboxylative arylation of imidazo1,2- a pyridine-3-carboxylic acids with (hetero)aryl halides. A few of the compounds synthesized using this protocol showed antibacterial activity against Staphylococcus aureus .
The Co(II)Cl2·6H2O catalyzed C–H activation/direct arylation of imidazo1,2‐apyridine with aryl/heteroaryl iodide is reported. The cost effective, ligand and additive free protocol using KOAc ...successfully afforded 3‐arylimidazo1,2‐apyridines in good yields. Imidazo1,2‐apyridines with electron withdrawing and electron donating substituents with various aryl iodides are well tolerated. The reaction is performed in a Screw‐top V‐Vial® to expedite the synthesis. The antibacterial 3‐naphthyl imidazo1,2‐apyridine is smoothly prepared using this protocol.
A practical protocol for the C‐3 arylation of imidazo1,2‐apyridines with aryl/heteroaryl iodides using Co(II)Cl2·6H2O is reported. The reaction can be performed in a Screw‐top V‐Vial® to expedite the synthesis.
The Co(II)Cl2·6H2O catalyzed C–H activation/direct arylation of imidazo1,2‐apyridine with aryl/heteroaryl iodide is reported. The cost effective, ligand and additive free protocol using KOAc ...successfully afforded 3‐arylimidazo1,2‐apyridines in good yields. Imidazo1,2‐apyridines with electron withdrawing and electron donating substituents with various aryl iodides are well tolerated. The reaction is performed in a Screw‐top V‐Vial® to expedite the synthesis. The antibacterial 3‐naphthyl imidazo1,2‐apyridine is smoothly prepared using this protocol.
A simple, mild, and ecofriendly protocol for a palladium-catalysed direct arylation of imidazo1,2-apyridines with aryl halides on water is reported. This protocol does not require any ligand and ...tolerate variety of functional groups on both the coupling partners. The simple base KOH is highly efficient in this transformation.
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•Direct arylation of imidazo1,2-apyridines with aryl halides on water.•Ligandless protocol.•Aryl iodides, bromides, and chlorides underwent successful arylation.
Novel inhibitors are needed to tackle tuberculosis. Herein, we report the 3‐aryl‐substituted imidazo1,2‐apyridines as potent antituberculosis agents. A small library of 3‐aryl‐substituted ...imidazo1,2‐apyridines was synthesized using direct arylation, followed by nitro reduction and finally Pd‐catalyzed C−N coupling reactions. The compounds thus obtained were evaluated against Mycobacterium tuberculosis H37Rv. Compound 26 was identified as an antituberculosis lead with a minimum inhibitory concentration of 2.3 μg/ml against M. tuberculosis H37Rv. This compound showed a selectivity index of 35. The docking of 26 in the active site of the M. tuberculosis cytochrome bc1 complex cytochrome b subunit (Mtb QcrB) revealed key π–π interactions of compound 26 with the Tyr389 and Trp312 residues of Mtb QcrB.
A facile strategy was developed for the synthesis of biologically important 4,5‐dihydropyrrolo1,2‐aquinoxalines and pyrrolo1,2‐aquinoxalin‐2‐ones by treating 2‐(1H‐pyrrol‐1‐yl)anilines with ...imidazo1,2‐apyridine‐3‐carbaldehyde or isatin, using amidosulfonic acid (NH3SO3) as a solid catalyst in water at room temperature. The protocol has been extended to electrophile ninhydrin. The catalyst could be recycled for six times without the loss of activity. The compounds were evaluated for their antituberculosis, antibacterial, and anticancer activities. It is worth noting that compounds 3d and 3e demonstrated a minimum inhibitory concentration value of 6.25 µM against Mycobacterium tuberculosis H37Rv, whereas compounds 3d, 3g, 5d, 5e, and 5i showed a remarkable inhibition of A549, DU145, HeLa, HepG2, MCF‐7, and B16‐F10 cell lines, respectively. Staphylococcus aureus was inhibited by compounds 5b, 5e, 5d, 5g, and 5l at 32 µg/ml.
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