Anti-inflammatory effects of novel barbituric acid derivatives in T lymphocytes

Antifibrotic Effects of a Barbituric Acid Derivative on Liver Fibrosis by Blocking the NF-κB Signaling Pathway in Hepatic Stellate Cells

“…Although there are some FDAapproved drugs used in treating multiple myeloma with the strategy to suppress NF-kB, theses agents have been thwarted by side effects including nephrotoxicity, neuropathy, and the malignancy (Mina et al, 2016). In previous study, a barbituric acid derivative was found to posse the ability to block IL-2 production in activated Jurkat T cells (Xu et al, 2016). In our animal study, we did not find any body weight lost, liver and kidney damage in BA-5 administrated mice group (Figure 7).…”

“…Although barbituric acid is not pharmacologically active, it can form a large variety of derivatives called barbiturates that have been used in many ways (Shahzad et al, 2016). Barbituric acid derivatives possess different biological activities, such as hypnotic (Shonle and Moment, 1923;Wisner, 1925), sedative (Kliethermes et al, 2004), anticonvulsant (Srivastava and Kumar, 2004), antimicrobial (Dhorajiya et al, 2014), antiviral (Marecki et al, 2019), anti-inflammatory (Xu et al, 2016), anticancer, and antitumor properties (Singh et al, 2009;Penthala et al, 2015;Laxmi et al, 2016). In 2011, a study showed that a novel barbituric and thiobarbituric acid derivative inhibited high-fat/high-calorie diet-induced nonalcoholic fatty liver disease in male Wistar rats .…”

Role of Phosphodiesterase 7 (PDE7) in T Cell Activity. Effects of Selective PDE7 Inhibitors and Dual PDE4/7 Inhibitors on T Cell Functions

“…The diminution in IL-2 production by BC12 was also observed in a study with primary human and murine T cells stimulated by anit-CD3/anti-CD28 antibodies or by PMA plus ionomycin, respectively. Additionally, both BC12 and BC12-4 inhibited T cell proliferation of murine T splenocytes [56].…”

“…PDE7 inhibitors belong to different chemical groups, with wide structural diversity, for example, thiadiazole derivatives [52], sulfonamide derivatives [42], thioxoquinazoline derivatives [53], pyrimidine-based inhibitors [54], furan derivatives [55], or barbituric acid derivatives [56].…”

“…Xu et al [56] identified barbituric acid derivatives as PDE7 inhibitors, and one of them, BC12 (IC 50 = 0.77 µM), exhibited a potent immunosuppressive effect. BC12 inhibited IL-2 production in the culture of Jurkat T cells stimulated with a combination of phorbol-12-myristate-13-acetate (PMA) and PHA.…”