Effect of sydnone SYD-1 on certain functions of LPS-stimulated macrophages

Abstract

In an earlier article, we demonstrated that sydnone SYD-1 (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) inhibits electron transport in the respiratory chain and uncouples oxidative phosphorylation, and postulated that these effects are probably involved in its antitumor activity. We now report the effect of SYD-1 on certain macrophage functions, considering the important role of these cells in inflammatory response and also the relevant anti-inflammatory activity reported for some sydnones. Incubation of macrophages with SYD-1 (5-100 μM) for 48 h did not affect the cell viability up to a concentration of 50 μM. However, at the highest concentration (100 μM), the compound decreased macrophage viability by ~20%. In assays involving 2 h and 24 h of incubation, SYD-1 (5-100 μM) did not affect the cell viability. The incubation of macrophages with the compound for 2 h promoted a dose-dependent reduction of phagocytic activity of up to ~65% (100 μM). SYD-1 (100 μM) was also able to increase the production of superoxide anion (~50%). In the absence of LPS, SYD-1 decreased NO production dose-dependently by up to ~80% (100 μM). When SYD-1 and LPS were incubated concomitantly, the decrease of NO promoted by SYD was the most pronounced, reaching up to ~98% at the same concentration (50 μM). SYD-1 dose-dependently suppressed IL-6 secretion by LPS-stimulated macrophages, reaching up to ~90% of inhibition at the highest concentration (100 μM). These results indicate that SYD-1 promotes effects similar to those described for anti-inflammatory and immunosuppressive drugs, thus motivating further studies to clarify the mechanisms involved in this activity.

First Hyperpolarizability of 1,3-Thiazolium-5-Thiolates Mesoionic Compounds

“…Among the push–pull organic systems known, the mesoionic compounds (MICs) deserve special attention because of their remarkable physical and chemical properties that enable applications as antioxidant, anti-inflammatory, antibacterial, and antitumor sumstances, as well as the large NL optical susceptibility as already proposed − and experimentally demonstrated. − Indeed, the MICs’ properties point to NL biophotonics as a possible avenue for future applications.…”

Sydnone 1: A Mesoionic Compound with Antitumoral and Haematological Effects In Vivo

“…The mesoionic compound Syd‐1 (fig. A ) was synthesized in the Department of Chemistry, Federal Rural University of Rio de Janeiro. N ‐(4‐chloro‐3‐nitrophenyl)‐sydnone.…”

“…Of the mesoionic compounds, 1,2,3‐oxadiazole‐5‐olates, also called sydnones, have been the most extensively studied . Sydnones have numerous pharmacological activities, including antibacterial, anti‐inflammatory, analgesic and antitumour effects . In addition to the pharmacological activities that have been attributed to these compounds, sydnones also have great importance because they act as precursors of bioactive molecules .…”

Mesoionic Sydnone: A Review in Their Chemical and Biological Properties

“…Studies proved that PLA2 inhibitors can be as potent as steroidal anti-inflammatory drugs due to the reduction of lipid mediators which were usually secreted as a response to tissue injury [56]. Others found that 3-(4-chloro-3-nitro) sydnone mimicked the anti-inflammatory and immunosuppressive agents by reducing phagocytic activity, increasing superoxide anion production, inhibiting the production of nitric oxide, and declining interleukin-6 (IL-6) levels in peritoneal macrophages [57].…”