Synthesis, biological evaluation and molecular dynamics simulation studies of novel diphenyl ethers.

Synthesis, biological evaluation and molecular dynamics simulation studies of novel diphenyl ethers. Med Chem. 2019 Mar 06;: Authors: Khade AB, Kar SS, Thomas AC, Tiwari A, Tiwari M, Vandana KE, Bhat P, Bhat GV, Shenoy GG Abstract A series of novel N-(1-(3-hydroxy-4-phenoxyphenyl)-3-oxo-3-phenylpropyl)acetamides and N-(3(3-hydroxy-4phenoxyphenyl)-3-oxo-1-phenylpropyl) acetamides were designed, synthesized, and evaluated against HepG2, A-549, MCF-7 and Vero cell lines. Among the tested compounds, compound 3d was most active (IC50 13.76 ± 0.43 µM) against A-549 cell line. Compounds 3d and 3g were found to be moderately active with IC50 30.56 ± 1.1 µM and 25.05 ± 0.8 µM respectively against MCF-7 cell line. Induction of antiproliferative activity of compound 3d and 6c was confirmed by AO/EB (acridine orange/ethidium bromide) nuclear staining method and also by DNA fragmentation study. Morphological analysis of A-549 cells treated with 3d and 6c clearly demonstrated the reduction of cell viability and induction of apoptosis. DNA fragmentation was observed as a characteristic of apoptosis in treated cells. Further, cell cycle analysis by flow cytometry confirmed that compounds 3d and 6c significantly arrested the cell cycle at the G0/G1 phase. Molecular docking study demonstrated that these compounds exhibit high affinity for the human fatty acid synthase (hFASN) target. Molecular dynamics simulation study of the most active compoun...
Source: Medicinal Chemistry - Category: Chemistry Authors: Tags: Med Chem Source Type: research