Conformationally locked thiosugars as potent alpha-mannosidase inhibitors: synthesis, biochemical and docking studies.
A series of thiosugar derivatives (thiolevomannosans) derived from mannose were synthesized and their inhibitory activity was tested against alpha-mannosidase (jack bean). These inhibitors were found to be more potent than the well-known inhibitors like kifunensine and deoxymannojirimycin based on docking and biochemical studies. The sulfone derivative 10 was shown to be the best inhibitor of alpha-mannosidase with the K(i) value of 350 nM.
Sivapriya
K
K
Department of Organic Chemistry, Indian Institute of Science, Bangalore, Karnataka, India.
Hariharaputran
S
S
Suhas
V L
VL
Chandra
N
N
Chandrasekaran
S
S
D002241:Carbohydrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013450:Sulfones / Q000737:chemistry; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*
D002241:Carbohydrates; D004791:Enzyme Inhibitors; D008024:Ligands; D013438:Sulfhydryl Compounds; D013450:Sulfones; D043323:alpha-Mannosidase; D012451:Safrole; C005746:sulfoxide