QSAR and Molecular Docking Studies on a Series of 1-Amino-5H-pyrido [4, 3-b]indol-4-carboxamides Acting as Janus Kinase 2 (JAK2) Inhibitors

Title:QSAR and Molecular Docking Studies on a Series of 1-Amino-5H-pyrido [4, 3-b]indol-4-carboxamides Acting as Janus Kinase 2 (JAK2) Inhibitors

Volume: 15 Issue: 2

Author(s): Basheerulla Shaik*, Satya P. Gupta, Tabassum Zafar and K. Anita

Affiliation:

• Department of Applied Sciences, National Institute of Technical Teachers' Training & Research, Shamla Hills, Bhopal- 462002,India

Keywords: Janus kinase 2 (JAK2) inhibitors, tyrosine kinase, quantitative structure-activity relationship study, docking study, ADMET, myeloproliferative disorders.

Abstract: Background: The Janus enzyme family is regulated by various cytokines together with interleukins, interferons, and hormones like glycoprotein, thromboprotein, and hormone. Metamorphosis and translocations in the Janus Kinase genes leading to constitutively active Janus Kinase proteins are associated with a variety of hematopoietic malignancies, comprising the myeloproliferative disorders, acute lymphoblastic leukemia, acute myeloid leukemia (JAK2, JAK1), acute megakaryoblastic leukemia (JAK2, JAK3). Hence the study of the inhibitors of Janus Kinase is desired.

Methods: Research and online content related to 1-amino-5H-pyrido [4,3-b]indol-4-carboxamide analogues (I) that were synthesized and evaluated for their JAK2 inhibitory activity is reviewed, and in order to design and develop still better and more effective JAK inhibitors, we have made Quantitative Structure Activity Relationship (QSAR), docking and ADMET studies on these compounds

Results: The best GA-MLR equation based on four descriptors along with statistical parameters is obtained using QSARINS software. Using the model expressed by this study we predicted some new compounds of high JAK2 inhibition potency. Each predicted compound has very high potency with which only a few compounds of existing series can match.

Conclusion: The QSAR and molecular modelling studies suggested that still better compounds can be designed if the flexibility of the molecules can be increased for which attempts can be made to have more saturated atoms in the molecules. Such a compound predicted by us was found to have interactions with the enzyme JAK2 almost in the same manner as the FDA approved compound, Momelotinib.

Cite this article as:

Shaik Basheerulla*, Gupta P. Satya , Zafar Tabassum and Anita K. , QSAR and Molecular Docking Studies on a Series of 1-Amino-5H-pyrido [4, 3-b]indol-4-carboxamides Acting as Janus Kinase 2 (JAK2) Inhibitors, Letters in Drug Design & Discovery 2018; 15 (2) . https://dx.doi.org/10.2174/1570180814666170605113844