Exploring structural requirements of imaging agents against Aβ plaques in Alzheimer's disease: a QSAR approach.
Exploring molecular imaging agents against the beta amyloid (Aβ) plaques for an early detection of Alzheimer's disease (AD) is one of the emerging research areas in medicinal chemistry. In the present in-silico study, a congeneric series of 44 imaging agents, including 17 positron emission tomography (PET) and 27 single photon emission computed tomography (SPECT) imaging agents, was utilized to understand the structural features required for having essential binding affinity against Aβ plaques. Here, 2D-quantitative structure-activity relationship (2D-QSAR) and group-based QSAR (G-QSAR) models have been developed using genetic function approximation (GFA) and validated using various statistical metrics. Both the models showed satisfactory performance signifying the reliability and robustness of the developed QSAR models. The vital information gained from both the QSAR models will be useful in developing new PET and SPECT imaging agents and also in predicting their binding affinity against Aβ plaques. The results of this study would be important in view of the widespread clinical applicability of the SPECT imaging agents, especially in the developing countries. In this study, we have also designed some imaging agents based on the information provided by the models. Some of these designed compounds were predicted to be similar to or more active than the most active imaging agents present in the original dataset.
Pravin
P
Ambure
Drug Theoretics and Cheminformatics Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India. kunalroy_in@yahoo.com.
Kunal
K
Roy
D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D013844:Thiazoles; C070845:2-phenylbenzothiazole