Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach.
Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds "N1" exhibited binding energy -9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine.
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdul Aziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia.
Abdul
0000-0001-6518-6131
A
Samad
Faculty of Pharmacy, University of Sydney, NSW 2006, Australia.
Moawiah M
MM
Naffaa
Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdul Aziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia.
Mohammed Afroz
MA
Bakht
Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ferozepur Road, Moga 142 001, India.
Manav
M
Malhotra
Department of Pharmacology, College of Pharmacy, Salman bin Abdul Aziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia.
Majid A
MA
Ganaie