1Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, PO Box No 17020, Jadavpur University, Kolkata 700 032, India.
2Department of Medicinal Chemistry, College of Pharmacy, 8–125 Weaver Densford Hall, 308, Harvard St SE, University of Minnesota, Minneapolis MN – 55455, USA.
*Corresponding author. E-mail address: tjjupharm@yahoo.com.
#Present Address: School of Biological Sciences, Nanyang Technolgical University, 60 Nanyang Drive Singapore 637551.
†Present address: Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48202, USA.
Potent and selective inhibitors of protein kinases are important against several neurodegenerative disorders such as cancers, diabetes and Alzheimer's disease. Quantitative structure activity relationship (QSAR) analysis have been performed on a series of indirubins, a family of bis-indoles that act as potent inhibitors of cyclin dependent kinases (CDKs) and glycogen synthase kinase-3 (GSK-3). The studies were carried out using 37 analogs. These analysis showed that the electronic interaction with the receptor and electronegativity of some atom played significant roles for inhibitory activity of indirubins against CDK1/cyclin B, whereas dispersive/van der Waals interaction as well as electronic interaction with the receptor played important role for the inhibitory activity of indirubins against GSK-3α/β. The approach provided the mapping of the pharmacophore of indirubins required for these types of inhibitions.
Indirubins, CDK, GSK-3, QSAR, ETSA, RTSA
