| Abstrakt: |
The NAD+-dependent histone deacetylase SIRT1 was shown to be associated with aging and longevity. A stilbene, resveratrol (RV) was shown to exert anti-aging activity by stimulating the SIRT1 activity. However, the utility of RV is limited by its low bioavailability and structural instability. It is thus envisaged to test imine stilbene (IMS) analogs of RV for their potential anti-aging activity. In the present study, molecular docking analysis of five IMS analogs (3a, 3b, 3c, 3d and 3e) against the SIRT1 protein has been carried out. All the five IMS analogs displayed enhanced binding affinity towards SIRT1; three out of five IMS analogs (3a, 3 b, 3e) showed significantly higher affinity with lower binding energies (−9.58, −9.54, and −9.82 kcal mol−1) than RV (−8.11 kcal mol−1). Further, experimental validation of anti-aging activity was performed by measuring the chronological life span in vitro using yeast and cellular replicative senescence (CRS) in mammalian cell line models. All IMS analogs extended the chronological life span in yeast as compared to untreated cells as well as RV treated cells. Enhanced anti-aging activity was also observed in an analogous mammalian cell line model upon treatment with either RV or IMS analogs. The results thus suggest that most of the IMS analogs tested may serve as potent drug lead molecules with anti-aging activity. [ABSTRACT FROM AUTHOR] |
