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QSAR, molecular docking and dynamics studies of quinazoline derivatives as inhibitor of phosphatidylinositol 3-kinase
Arba M.a, Ruslina, Kalsum W.U.a, Alroem A.a, Muzakkar M.Z.a, Usman I.a, Tjahjono D.H.b
a Faculty of Pharmacy, Halu Oleo University, Kendari, 93232, Indonesia
b School of Pharmacy, Institut Teknologi Bandung, Bandung, 40132, Indonesia
[vc_row][vc_column][vc_row_inner][vc_column_inner][vc_separator css=”.vc_custom_1624529070653{padding-top: 30px !important;padding-bottom: 30px !important;}”][/vc_column_inner][/vc_row_inner][vc_row_inner layout=”boxed”][vc_column_inner width=”3/4″ css=”.vc_custom_1624695412187{border-right-width: 1px !important;border-right-color: #dddddd !important;border-right-style: solid !important;border-radius: 1px !important;}”][vc_empty_space][megatron_heading title=”Abstract” size=”size-sm” text_align=”text-left”][vc_column_text]© 2018 Muhammad Arba et al.Phosphatidylinositol 3-kinase (PI3K) plays a prominent role in regulating various crucial cellular functions. Many studies have indicated the involvement of PI3K in tumorigenesis. In the current study, thirty-one quinazoline derivatives were utilized to build a Quantitative Structure-Activity Relationship (QSAR) model which correlates structural feature with PI3K inhibition. The statistically robust QSAR model is pIC50 = 2.515 + 0.000005 (AM1_Eele) + 0.004 (AM1_HF) + 1.170 (AM1_LUMO) – 0.117 (apol) + 0.003 (ASA_H) with a leave-one-out cross-validation coefficient (q2) of 0.6058 and external validation (R2pred) of 0.7725. A novel compound (SC25) was proposed based on the validated QSAR model. Molecular docking of the ligand on PI3K revealed the similar binding mode of SC25 and parent compound ((S)-C5) as well as native ligand (2NQ). Molecular dynamics simulation of 40 ns confirmed the conformational stability of each SC25, (S)-C5, and 2NQ, complexed with PI3K. Prediction of affinity using MMPBSA method revealed that SC25 has a comparable affinity with that of (S)-C5 and better than that of 2NQ.[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Author keywords” size=”size-sm” text_align=”text-left”][vc_column_text][/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Indexed keywords” size=”size-sm” text_align=”text-left”][vc_column_text]Docking,MM-PBSA,Molecular dynamics simulation,Phosphatidylinositol 3-kinase,QSAR,Quinazoline[/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”Funding details” size=”size-sm” text_align=”text-left”][vc_column_text][/vc_column_text][vc_empty_space][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][vc_empty_space][megatron_heading title=”DOI” size=”size-sm” text_align=”text-left”][vc_column_text]https://doi.org/10.7324/JAPS.2018.8501[/vc_column_text][/vc_column_inner][vc_column_inner width=”1/4″][vc_column_text]Widget Plumx[/vc_column_text][/vc_column_inner][/vc_row_inner][/vc_column][/vc_row][vc_row][vc_column][vc_separator css=”.vc_custom_1624528584150{padding-top: 25px !important;padding-bottom: 25px !important;}”][/vc_column][/vc_row]