3D-QSAR analysis of anilinoquinoline inhibitors of colony stimulating factor-1 kinase (cFMS): implementation of field-based molecular alignment

• Published in: Medicinal chemistry research Vol. 22; no. 11; pp. 5167 - 5183
• Main Authors: Kumari, Archana, Kaur, Maninder, Bahia, Malkeet Singh, Silakari, Om
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.11.2013
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Original Research; Pharmacology/Toxicology; Colony-stimulating factor-1 receptor (cFMS); Rheumatoid arthritis; Atom-based 3D-QSAR; Field-based alignment
• ISSN: 1054-2523; 1554-8120
• DOI: 10.1007/s00044-013-0513-8

Colony-stimulating factor-1 receptor (cFMS) serves as a binding site for colony-stimulating factor-1 and is primarily involved in the growth and differentiation of monocytes and macrophages. This crucial function of cFMS links it to various immune system-related disease conditions, such as rheumatoid arthritis, cancer, and immune nephritis. Hence, the potent inhibitors of cFMS may serve novel therapeutic benefits for the treatment of mentioned disease conditions. In the present study, a set of 46 anilinoquinoline derivatives was utilized to perform atom-based 3D-QSAR analysis. The best 3D-QSAR model was selected on the basis of the highest value of Q test 2 , i.e., 0.535. The selected model also displayed high values of R train 2 (0.974), Pearson- r (0.826), and the lowest value of SD (0.099). The contour plots generated for different properties helped to understand biological activity variation pattern with structural changes in molecule at appropriate sites. Therefore, the selected 3D-QSAR model and information revealed from it would provide beneficial guidance for the designing of new potent cFMS inhibitors that can further be explored as novel therapeutic agents for various immune system-related disease conditions.