Naslov
Use of connectivity index and simple topological parameters for estimating the inhibition potency of acetylcholinesterase

Autori
Miličević, Ante ; Šinko, Goran

Izvornik
SAUDI PHARMACEUTICAL JOURNAL (1319-0164) 30 (2022), 4; 369-376

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Dementia ; Alzheimer's disease ; Inhibitor ; Acetylcholinesterase ; QSAR descriptor

Sažetak
Acetylcholinesterase (AChE) has proven to be an effective drug target in the treatment of neurodegenerative diseases such as Alzheimer’s, Parkinson’s and dementia. We developed a novel QSAR regression model for estimating potency to inhibit AChE, pKi, on a set of 75 structurally different compounds including oximes, N- hydroxyiminoacetamides, 4-aminoquinolines and flavonoids. Although the model included only three simple descriptors, the valence molecular connectivity index of the zero-order, 0χv, the number of 10-membered rings (nR10) and the number of hydroxyl groups (nOH), it yielded excellent statistics (r = 0.937, S.E. = 0.51). The stability of the model was evaluated when an initial set of 75 compounds was broadened to 165 compounds in total, with the increase of the range of pKi (exp) from 6.0 to 10.2, yielding r = 0.882 and S.E. = 0.89. The predictive power of the model was evaluated by calculating pKi values for 55 randomly chosen compounds (S.E.test = 0.90) from the calibration model created on other 110 compounds (S.E. = 0.89), all taken from the pool of 165 compounds.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA