Synthesis and Biological Evaluation of Substituted N‐[3‐(1H‐Pyrrol‐1‐yl)methyl]‐1,2,5,6‐tetrahydropyridin‐1‐yl]benzamide/benzene Sulfonamides as Anti‐Inflammatory Agents

Abstract

The pharmacological activities of tetrahydropyridine (THP) derivatives are dependent on the substituent ring moiety. In this study, we investigate the anti-inflammatory activities of 12 newly synthesized substituted N-[3-(1H-pyrrol-1-yl)methyl]-1,2,5,6-tetrahydrobenzamide/benzene sulfonamides (9a–l) in murine BV-2 microglial cells. All compounds were initially screened for attenuation of nitric oxide (NO) production in lipopolysaccharide (LPS) (1 μg/mL)-activated microglial cells. The data show that only SO2-substituted THPs were effective at sub-lethal concentrations (IC50 values of 12.92 μM (9i), 14.64 μM (9j), 19.63 μM (9k)) relative to L-N6-(1-iminoethyl)lysine positive control (IC50 = 3.1 μM). The most potent SO2-substituted compound (9i) also blocked the LPS-inducible nitric oxide synthase (iNOS) and attenuated the release of several cytokines including IL-1α, IL-10, and IL-6. These findings establish the moderate immunomodulating effects of SO2-substituted THP derivatives.

Synthesis and pro-apoptotic effects of new sulfonamide derivatives via activating p38/ERK phosphorylation in cancer cells

“…In recent times, there has been an increase in studies regarding the substances containing sulfonamide fragment because of their potential applications such as for coordination chemistry 18 , medicinal chemistry 19 , catalyst chemistry 20 , chemical luminescence 21 and analytical chemistry fields 22 . On the other hand, sulfonamide compounds are known to contain inherent pharmacological properties such as antimicrobial 23 , anti-inflammatory 24 , anti-viral 25 , anti-proliferative 26 , angiogenesis 27 and enzyme inhibitory (carbonic anhydrase) activities 28 . Therefore, based on these findings, sulfonamide compounds were synthesized by the reaction of sulfonamide fragments; N-(2-amino-5-benzoylphenyl)-4-nitrobenzenesulfonamide hydrochloride (1), N-(quinolin-8-yl)-4-nitro-benzenesulfonamide hydrochloride (2), N-(pyridine-2-ylmethyl)-4-nitro-benzenesulfonamide hydrochloride (3) with3,4-diaminobenzophenone, 8-aminoquinoline or 2-picoylamine and 4-nitrobenzensulfonyl chloride, respectively and we tested the effects compounds on cell viability, pro-apoptotic gene expression and of p38/ERK activation.…”

Substituted Tetrahydroisoquinolines as Microtubule-destabilizing Agents in Triple Νegative Human Breast Cancer Cells

“…Synthesis of THIQs has been previously described (16–18) for GM-3-121, with additional information on the synthesis for GM-4-53 as follows General procedure for the synthesis of 2-amino-7-hydroxyisoquinolinium 2,4,6-trimethylbenzenesulfonate: O-mesitylene sulfonyl hydroxylamine (MSH) (3) was used to prepare the N -amino salt as an aminating agent as described (19). An ice cooled solution of 7-hydroxyisoquinoline (2.0 g, 13.78 mmol) in 30 ml of dry methylene chloride, and 15 ml of dry methanol was added drop wise to O -mesitylenesulfonylhydroxylamine (2.97 g, 13.78 mmol) in 10 ml of dry methylene chloride over 5 min with stirring.…”

“…In our recent studies, we reported the synthesis of THIQs by N -amination of isoquinoline using hydroxylamine-O-sulfonic acid followed by ylide formation and reduction, which yielded the desired, N -substituted THIQs (16–18). In this study, we evaluate the effects of these THIQs on growth parameters in TNBC cells.…”

Recent Functionalizations of Primary Sulfonamides

“…The sulfonamide moiety is a common building block in organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13][14] and an essential functional group in drug design. [15][16][17][18][19] Sulfonamides have a wide range of medical applications due to their anti-inflammatory, [15][16][17] antibacterial, [18][19][20][21] antimicrobial, [22][23][24] anticancer, [25][26][27][28][29][30][31] antimalarial, 32 and antipsychotic activities. 33 They have been reported to be inhibitors of DNA double-strand break repair, 34 dual angiotensin II and endothelin A receptor antagonists, 35 cyclooxygenase-2 inhibitors associated with different diseases, [36][37][38][39][40][41][42]…”