An article Chemical synthesis, microbial transformation and biological evaluation of tetrahydroprotoberberines as dopamine D1/D2 receptor ligands WOS:000465176600016 published article about BERBERINE ANALOGS; L-STEPHOLIDINE; ANTAGONIST; D-1; PHARMACOLOGY; DISCOVERY; ECOPIPAM; (-)-STEPHOLIDINE; IDENTIFICATION; DERIVATIVES in [Ge, Haixia; Qiang, Kun; Chen, Chao; Sun, Laiyu] Huzhou Univ, Sch Life Sci, Huzhou 313000, Peoples R China; [Zhang, Yan; Zhang, Jian] China Pharmaceut Univ, Sch Tradit Chinese Pharm, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China; [Yang, Zhuo; Chen, Ming] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Biochem & Cell Biol, Chem Biol Core Facil, Shanghai 200031, Peoples R China in 2019.0, Cited 42.0. Formula: C7H6O2. The Name is 3-Hydroxybenzaldehyde. Through research, I have a further understanding and discovery of 100-83-4
Dopamine D1/D2 receptors are important targets for drug discovery in the treatment of central nervous system diseases. To discover new and potential D1/D2 ligands, 17 derivatives of tetrahydroprotoberberine (THPB) with various substituents were prepared by chemical synthesis or microbial transformation using Streptomyces griseus ATCC 13273. Their functional activities on D1 and D2 receptors were determined by cAMP assay and calcium flux assay. Seven compounds showed high activity on D1/D2 receptor with low IC50 values less than 1 mu M. Especially, top compound 5 showed strong antagonistic activity on both D1 and D2 receptor with an IC50 of 0.391 and 0.0757 mu M, respectively. Five compounds displayed selective antagonistic activity on D1 and D2 receptor. The SAR studies revealed that (1) the hydroxyl group at C-9 position plays an important role in keeping a good activity and small or fewer substituents on ring D of THPBs may also stimulate their effects, (2) the absence of substituents at C-9 position tends to be more selective for D2 receptor, and (3) hydroxyl substitution at C-2 position and the substitution at C-9 position may facilitate the conversion of D1 receptor from antagonist to agonist. Molecular docking simulations found that Asp 103/Asp 114, Ser 107/Cys 118, and Trp 285/Trp 386 of D1/D2 receptors are the key residues, which have strong interactions with the active D1/D2 compounds and may influence their functional profiles.
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Reference:
Indole alkaloid derivatives as building blocks of natural products from Bacillus thuringiensis and Bacillus velezensis and their antibacterial and antifungal activity study,
,Preparation of Indole Containing Building Blocks for the Regiospecific Construction of Indole Appended Pyrazoles and Pyrroles