Manikandan Alagumuthu1, Sivakumar Arumugam2. 1. Department of Biotechnology, School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, 632014, India. 2. Department of Biotechnology, School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, 632014, India. siva_kumar.a@vit.ac.in.
Abstract
PURPOSE: Substituted 2-(4-phenylquinolin-2-yl) phenols (PQPDs) emerged as the inhibitors of phosphoinositide 3-kinase (PI3K) and anticancer agents. METHOD: PI3K inhibition was assessed by competitive ELISA. Anticancer activity was evaluated against breast cancer (MCF-7), skin cancer (G-361), and colon cancer (HCT 116) cell lines. RESULTS: In PI3 Kinase assay, PQPDs 4c, 4d, and 4k were inactive with IC50 >5 µM. IC50 for 4a, 4b, 4f-h, and 4j was ≥0.05 µM. Rest PQPDs IC50 was <1.0 µM. Anticancer activity found selective toward breast cancer (MCF-7); 4a, 4b, and 4j were showed excellent inhibitory (73.95, 68.36, and 70.06%) and IC50 1.16 µM (4a), 2.07 µM (4b), 1.021 µM (4f) and 1.981 µM (4j) while the standard (Doxorubicin) found with IC50 1.812 µM (72% inhibition). PQPDs were docked into the active site of PI3 Kinase p110α (PDB ID: 2RD0). Docking results suggested the hydrophobic interactions in PI3K binding pocket conquered affinity of the most favorable binding ligands [4a, 4b: inhibitory constant (ki) = 53.33, 41.23 pM]. CONCLUSION: PI3K assay and cancer cell line experimental results ensured that the inhibitory and anticancer activity potentials of PQPDs are more selective toward breast cancer treatments. PQPDs 4a, 4b, 4f, 4g, and 4j were displayed potent PI3 Kinase and anticancer activities. SAR studies demonstrated PQPDs as the PI3K precise inhibitors with the impending to treat various cancers.
PURPOSE: Substituted 2-(4-phenylquinolin-2-yl) phenols (PQPDs) emerged as the inhibitors of phosphoinositide 3-kinase (PI3K) and anticancer agents. METHOD: PI3K inhibition was assessed by competitive ELISA. Anticancer activity was evaluated against breast cancer (MCF-7), skin cancer (G-361), and colon cancer (HCT 116) cell lines. RESULTS: In PI3 Kinase assay, PQPDs 4c, 4d, and 4k were inactive with IC50 >5 µM. IC50 for 4a, 4b, 4f-h, and 4j was ≥0.05 µM. Rest PQPDs IC50 was <1.0 µM. Anticancer activity found selective toward breast cancer (MCF-7); 4a, 4b, and 4j were showed excellent inhibitory (73.95, 68.36, and 70.06%) and IC50 1.16 µM (4a), 2.07 µM (4b), 1.021 µM (4f) and 1.981 µM (4j) while the standard (Doxorubicin) found with IC50 1.812 µM (72% inhibition). PQPDs were docked into the active site of PI3 Kinase p110α (PDB ID: 2RD0). Docking results suggested the hydrophobic interactions in PI3K binding pocket conquered affinity of the most favorable binding ligands [4a, 4b: inhibitory constant (ki) = 53.33, 41.23 pM]. CONCLUSION: PI3K assay and cancer cell line experimental results ensured that the inhibitory and anticancer activity potentials of PQPDs are more selective toward breast cancer treatments. PQPDs 4a, 4b, 4f, 4g, and 4j were displayed potent PI3 Kinase and anticancer activities. SAR studies demonstrated PQPDs as the PI3K precise inhibitors with the impending to treat various cancers.