Exploring Structure-Activity Relationship in Tacrine-Squaramide Derivatives as Potent Cholinesterase Inhibitors

quantitative structure activity relationship and docking studies on imidazole derivatives as p-glycoprotein inhibitors

Structure-activity relationship study of 4-(thiazol-5-yl)benzoic acid derivatives as potent protein kinase CK2 inhibitors.

Two classes of modified analogs of 4-(thiazol-5-yl)benzoic acid-type CK2 inhibitors were designed. The azabenzene analogs, pyridine- and pyridazine-carboxylic acid derivatives, showed potent protein kinase CK2 inhibitory activities [IC50 (CK2α)=0.014-0.017μM; IC50 (CK2α')=0.0046-0.010μM]. Introduction of a 2-halo- or 2-methoxy-benzyloxy group at the 3-position of the benzoic acid moiety maintai...

Effects of Cholinesterase Inhibitors Tacrine and Metrifonate on Exploratory Activity in Rats with Induced Hypoxia

Dementia is a common symptom of many degenerative brain diseases. The cholinesterase inhibitors are widely recommended for the treatment of Alzheimer’s disease and different kind of dementia to improve memory functions. Tacrine is the first drug from this group. Metrifonate has been used as an antihelminthic in tropical countries for more than 30 years, and even recently has been suggested as a...

Phloroglucinol Derivatives as Potent Photosystem II Inhibitors

Studies on structure/activity relationships o f phloroglucinol derivatives tha t had been de­ signed based on the structures o f grandinol and hom ograndinol. potent photosystem II (PS II) inhibitors in Eucalyptus grandis, revealed th a t two electron-withdraw ing groups which differ by their electron-w ithdraw ing pow er on a phloroglucinol nucleus were essential for activity. A larger differe...

Structure–Activity Relationship Study Reveals ML240 and ML241 as Potent and Selective Inhibitors of p97 ATPase

To discover more potent p97 inhibitors, we carried out a structure-activity relationship study of the quinazoline scaffold previously identified from our HTS campaigns. Two improved inhibitors, ML240 and ML241, inhibit p97 ATPase with IC(50) values of 100 nM. Both compounds inhibited degradation of a p97-dependent but not a p97-independent proteasome substrate in a dual-reporter cell line. They...