(2S)-2-Amino-4-(butylsulfonimidoyl)butanoic acid (BD136012) is a building block containing a sulfoximine group. Several CDK and ATR inhibitors have exemplified the utilization of the NH sulfoximine group as abioisostere for a sulfonamide group to overcome the main project hurdles of aqueous solubility, sulfonamide-mediated off-target activity and IP. Moreover, its NH group could be expediently further functionalized through Buchwald-Hartwig coupling reaction and multifarious nucleophilic reactions.. Recommended Products is: 4381-25-3 and 1621962-30-8.
Authors have synthesized a series of novel substituted sulfonyl ethylenediamine (en) RuII arene complexes 1-8 of [(¦Ç6-arene)Ru(R1-SO2-EnBz)X], where the arene is benzene, HO(CH2)2O-Ph or biphenyl (biph), X = Cl or I, and R1 is Ph, 4-Me-Ph, 4-NO2-Ph or dansyl. The ‘piano-stool’ structure of complex 3, [(¦Ç6-biph)Ru(4-Me-phenyl-SO2-EnBz)I], was confirmed by x-ray crystallog. The values of their aqua adducts were determined to be high (9.1 to 9.7). Complexes 1-8 have antiproliferative activity against human A2780 ovarian, and A549 lung cancer cells with IC50 values ranging from 4.1 to >50¦ÌM, although, remarkably, complex 7 [(¦Ç6-biph)Ru(phenyl-SO2-EnBz)Cl] was inactive towards A2780 cells, but as potent as the clin. drug cisplatin towards A549 cells. All these complexes also showed catalytic activity in transfer hydrogenation (TH) of NAD+ to NADH with sodium formate as hydride donor, with TOFs in the range of 2.5-9.7 h-1. The complexes reacted rapidly with the thiols glutathione (GSH) and N-acetyl-L-cysteine (NAC), forming dinuclear bridged complexes [(¦Ç6-biph)2Ru2(GS)3]2- or [(¦Ç6-biph)2Ru2(NAC-H)3]2-, with the liberation of the diamine ligand which was detected by LC-MS. In addition, the switching on of fluorescence for complex 8 in aqueous solution confirmed release of the chelated DsEnBz ligand in reactions with these thiols. Reactions with GSH hampered the catalytic TH of NAD+ to NADH due to the decomposition of the complexes. Co-administration to cells of complex 2 [(¦Ç6-biph)Ru(4-Me-phenyl-SO2-EnBz)Cl] with L-buthionine sulfoximine (L-BSO), an inhibitor of GSH synthesis, partially restored the anticancer activity towards A2780 ovarian cancer cells. Complex 2 caused a concentration-dependent G1 phase cell cycle arrest, and induced a significant level of reactive oxygen species (ROS) in A2780 human ovarian cancer cells. The amount of induced ROS decreased with increase in GSH concentration, perhaps due to the formation of the dinuclear Ru-SG complex.
Effect of cysteine thiols on the catalytic and anticancer activity of Ru(II) sulfonyl-ethylenediamine complexes. Recommended basis is Sulfoximine, Bioisosteric. Products is: https://www.ambeed.com/products/50578-18-2.html, 145026-07-9
Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem