QSAR study about ATP-sensitive potassium channel activation of cromakalim analogues using CP-MLR approach.
The structure-activity models of the myorelaxant activity of the cromakalim analogues have been investigated with nearly 470 topological descriptors from DRAGON software using Combinatorial Protocol in Multiple Linear Regression (CP-MLR). Among the descriptor classes considered in the study, the binding affinity is correlated with simple functional (FUN), topological (TOPO), atom centered fragments (ACF), empirical (EMP), modified Burden eigenvalues (BCUT), Galvez topological charge indices (GVZ), 2D-autocorrelation (2D-AUTO) and constitutional (CONS) descriptors. The models developed, and the participating descriptors suggest that the substituent groups of 4,6-disubstituted-2,2-dimethylchromans hold scope for further modification in the optimization of activity. The higher path lengths rich in polarizability and lower path length rich in atomic mass in addition to the lower charge indices of the molecule are beneficiary to the activity. The participating descriptors also suggested that certain structural features such as carbon atoms attached to the heteroatom by single or multiple bonding, and lesser or 'no' branching in a molecule are helpful to augment the activity.
Sharma
Susheela
S
Department of Engineering Chemistry, Sobhasaria Engineering College, Sikar 332 021, India.
Prabhakar
Yenamandra S
YS
Singh
Prithvi
P
Sharma
Brij Kishore
BK
D000818:Animals; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D019806:Cromakalim / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D054086:KATP Channels / Q000819:agonists* / Q000378:metabolism; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D051381:Rats
D054086:KATP Channels; D019806:Cromakalim