Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity
Dar, AM; Shamsuzzaman, AM; Gatoo, MA
| HERO ID | 3173118 |
|---|---|
| In Press | No |
| Year | 2015 |
| Title | Synthesis of new steroidal imidazo [1,2-a] pyridines: DNA binding studies, cleavage activity and in vitro cytotoxicity |
| Authors | Dar, AM; Shamsuzzaman, AM; Gatoo, MA |
| Journal | Steroids |
| Volume | 104 |
| Page Numbers | 163-175 |
| Abstract | A one-pot strategy for the catalytic synthesis of series of new 5α-cholestan-6-spiro-5'-phenylamino-2H-imidazo [1',2'-a] pyridines (4-14) has been investigated. The synthesized products were obtained in good yields (85-90%) and the protocol uses Multi-component Reaction (MCR) involving steroidal ketones, 2-aminopyridines, isocyanides and propylphosphonic anhydride (®T3P) as a catalyst. After characterization by spectral and analytical data, the interaction studies of compounds (4-6) with DNA were studied by UV-vis, fluorescence spectroscopy, gel electrophoresis and molecular docking. The compounds bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb; 2.35×10(4), 3.71×10(4) and 3.24×10(4) M(-1), respectively, indicating the higher binding affinity of compound 5 towards DNA. Gel electrophoresis showed the concentration dependent cleavage activity of compounds 4-6 with DNA. Molecular docking studies suggested that compounds bind through minor groove to DNA. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay depicted promising anti-proliferative activity of compound 4-9 against different given cancer cells. In Western blotting, the expressions of relevant apoptotic markers depicted an apoptosis by steroidal imidazopyridines in A549 cells. Annexin V-FITC/PI staining data indicated that compounds could effectively induce apoptosis in A549 cells in a dose-dependent manner. FACS analysis shows that the compound 6 bring about cell cycle arrest at 2.62 μM concentration. |
| Doi | 10.1016/j.steroids.2015.09.010 |
| Pmid | 26433147 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |