Disulfide linked pyrazole derivatives inhibit phagocytosis of opsonized blood cells

Estimation of the Modulatory Roles of Thieno [2,3-c] Pyrazole Compounds Versus the Toxicity of 4-Nonylphenol in African Catfish (Clarias gariepinus)

“…A significant decrement was noticed in the blood platelet count together with eosinophilia in 4-NP intoxicated African catfish in a harmony with the findings detected by [20]. All thienopyrazole compounds except compound 1 antagonized the thrombocytopenia induced by 4-NP perhaps by prolongation of survival, reduction of turnover, and inhibition of phagocytosis [30,31]. With exclusion of thienopyrazole compounds 1, 2, and 3, the remaining ones succeeded to overcome the 4-NP-mediated eosinophilia as matched with prevention of eosinophil infiltration in actively sensitized guinea pigs and Brown Norway rats by YM-58483, another pyrazole derivative [32].…”

Small molecule phagocytosis inhibitors for immune cytopenias

“…Most compounds tested did not significantly affect the viability of the monocytes. We have thus embarked on making and iteratively exploring the structure-activity relationships of several sulfhydryl-and disulfide-containing derivatives of the pyrazole-containing lead identified in earlier studies using the MMA [46]. Five leads were identified, which were only active as disulfide-bridged dimers and not in their monomeric form, with phagocytosis inhibitory activity in low-μM concentration range.…”

“…[12]. (C) Small molecule inhibitors of phagocytosis [46,47] could mimic IVIg-mediated Fc blockade by interacting with and inhibiting the activating Fc receptors on macrophages, or, alternatively, by inhibiting downstream signaling pathways driving Fc-mediated phagocytosis.…”

“…Five leads were identified, which were only active as disulfide-bridged dimers and not in their monomeric form, with phagocytosis inhibitory activity in low-μM concentration range. The most promising lead, a disulfide-bridged derivative, 1,2-bis(3-methyl-1-phenyl-1H-pyrazol-5-yl)disulfane, inhibited phagocytosis in vitro with an IC 50 of 100 nM [46]. Our subsequent work with this compound led us to explore derivatives with the disulfide bond removed, to minimize loss of the drug due to oxidation/reduction reactions with non-targeted proteins, identifying several leads with more favorable drug-like properties and phagocytosis inhibition activities of up to 58% at test concentrations of 5 μM [47].…”

Facile synthesis of novel monocyclic trans- and cis-3-oxo/thio/seleno-4-pyrazolyl-β-lactams

“…7 Bonesi et al 8 synthesized a substituted pyrazole and investigated their potential activity as inhibitors of angiotensin coverting enzyme (ACE). In literature, several reports have demonstrated substituted pyrazole and their derivatives as inhibitors of GSK3β Glycogen synthase kinase, 9 VEGFR2 kinase, 10 tyrosinase, 11 phagocytosis of opsonized blood cells 12 and arylamine N-acetyltransferase. 13 Bondock et al, 14 Radi et al, 15 Sahu et al, 16 Barsoum et al 17 and Burguete et al 18 have synthesized a series of substituted pyrazole and their derivatives possess antifungal, antimicrobial, antibacterial and anti-inflammatory activities.…”