132912-80-2Relevant articles and documents
Development of phenylthiourea derivatives as allosteric inhibitors of pyoverdine maturation enzyme PvdP tyrosinase
Dekker, Frank J.,Quax, Wim J.,Voet, Julian M.,Wibowo, Joko P.,Xiao, Zhangping
, (2020)
Infections caused by Pseudomonas aeruginosa become increasingly difficult to treat because these bacteria have acquired various mechanisms for antibiotic resistance, which creates the need for mechanistically novel antibiotics. Such antibiotics might be developed by targeting enzymes involved in the iron uptake mechanism because iron is essential for bacterial survival. For P. aeruginosa, pyoverdine has been described as an important virulence factor that plays a key role in iron uptake. Therefore, inhibition of enzymes involved in the pyoverdine synthesis, such as PvdP tyrosinase, can open a new window for the treatment of P. aeruginosa infections. Previously, we reported phenylthiourea as the first allosteric inhibitor of PvdP tyrosinase with high micromolar potency. In this report, we explored structure-activity relationships (SAR) for PvdP tyrosinase inhibition by phenylthiourea derivatives. This enables identification of a phenylthiourea derivative (3c) with a potency in the submicromolar range (IC50 = 0.57 + 0.05 μM). Binding could be rationalized by molecular docking simulation and 3c was proved to inhibit the bacterial pyoverdine production and bacterial growth in P. aeruginosa PA01 cultures.
Facile synthesis of phthalidyl fused spiro thiohydantoins through silica sulfuric acid induced oxidative rearrangement of ninhydrin adducts of thioureas
Mandal, Subhro,Pramanik, Animesh
, (2019/12/24)
A one-pot three-component sequential synthetic protocol produces structurally and biologically important phthalidyl fused spiro N,N′-disubstituted thiohydantoins from readily available aromatic isothiocyanates, primary amines and ninhydrin. In this three-step synthesis while the initial two steps are catalyst-free, in the final step silica sulfuric acid (SSA) induces an oxidative rearrangement in [3.3.0]-bicyclic 1,2-diol adducts of ninhydrin and thioureas under solvent-free condition to generate the final products spiro-fused thiohydantoins. The adequate acidity of SSA in cooperation with moderate oxidizing property promotes a facile oxidative rearrangement in 1,2-diol intermediates to produce the spiro-fused thiohydantoins with diverse functionalities. Easy recyclability of SSA, good to excellent yield of the products, wider substrate scope, shorter reaction time, solvent-free two steps out of three and high atom economy make this method attractive and practicable.
