Synthesis of New Tricyclic and Tetracyclic Fused Coumarin Sulfonate Derivatives and Their Inhibitory Effects on LPS-Induced Nitric Oxide and PGE2 Productions in RAW 264.7 Macrophages: Part 2 was written by El-Gamal, Mohammed I.;Lee, Woo-Seok;Shin, Ji-Sun;Oh, Chang-Hyun;Lee, Kyung-Tae;Choi, Jungseung;Myoung, Nohsun;Baek, Daejin. And the article was included in Archiv der Pharmazie (Weinheim, Germany) in 2016.Safety of 4-Chlororesorcinol The following contents are mentioned in the article:
The synthesis of a new series of 21 fused coumarin derivatives is described, and the biol. evaluation of their in vitro antiinflammatory effects as inhibitors of lipopolysaccharide (LPS)-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in RAW 264.7 macrophages. The target compounds were first tested for cytotoxicity to determine a non-toxic concentration for antiinflammatory screening, so that the inhibitory effects against NO and PGE2 production would not be caused by cytotoxicity. Compounds 1f (2-methoxy-6-oxo-6,7,8,9,10,11-hexahydrocyclohepta[c]chromen-3-yl 4-methylbenzenesulfonate) and 1p (2-methoxy-6-oxo-7,8,9,10,11,12-hexahydro-6H-cycloocta[c]chromen-3-yl 4-methylbenzenesulfonate) were the most active PGE2 inhibitors with IC50 values of 0.89 and 0.95 μM, resp. Western blot and cell-free COX-2 screening showed that their effects were due to inhibition of both COX-2 protein expression and COX-2 enzyme activity. Their IC50 values against the COX-2 enzyme were 0.67 and 0.85 μM, resp., which is more potent than etoricoxib. The selectivity indexes of compounds 1f and 1p against COX-2 compared to COX-1 were 41.1 and 42.5, resp. Compound 1f showed strong inhibitory effects at 5 μM concentration on COX-2 mRNA expression in LPS-induced RAW 264.7 macrophages. Moreover, the tricyclic compounds 1l (6-oxo-7,8,9,10,11,12-hexahydro-6H-cycloocta[c]chromen-3-yl 4-fluorobenzenesulfonate) and 1n (2-methoxy-6-oxo-7,8,9,10,11,12-hexahydro-6H-cycloocta[c]chromen-3-yl propane-1-sulfonate) as well as the tetracyclic analog 1u were the most potent NO inhibitors, with one-digit micromolar IC50 values. They showed dose-dependent inhibition of inducible nitric oxide synthase (iNOS) protein expression. The tetracyclic derivative 1u was the most potent inhibitor of NO production It also exhibited a strong inhibitory effect on iNOS mRNA expression in LPS-induced RAW 264.7 macrophages. This study involved multiple reactions and reactants, such as 4-Chlororesorcinol (cas: 95-88-5Safety of 4-Chlororesorcinol).
4-Chlororesorcinol (cas: 95-88-5) belongs to organic chlorides. An organic chloride is an organic compound containing at least one covalently bonded atom of chlorine. Their wide structural variety and divergent chemical properties lead to a broad range of names and applications. The haloform reaction, using chlorine and sodium hydroxide, is also able to generate alkyl halides from methyl ketones, and related compounds. Chloroform was formerly produced thus.Safety of 4-Chlororesorcinol
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics