Structure of Scheme 2 compounds with their elemental property, docking score, MM-GBSA binding energy (ΔG_bind) and enzyme-based inhibition activity. The biological evaluation of enzyme-based inhibitory activity of test compounds at 10 μm concentration was obtained against recombinant human Sirt1, n = 3, and the results were represented as the mean of three independent experiments^a.

Comp.	R	R1	R2/R3	Mol. mass	Static docking Sirt1 (kcal mol−1)	IF guided docking Sirt1		% inhibition at 10 μM Sirt1
						Dock score (kcal mol−1)	ΔGbind (kcal mol−1)
13a	–H	–OMe	–H	375.42	−7.42	−6.54	−47.19	<30
13b		–OMe	–H	389.44	−7.64	−6.18	−46.74	<30
13c		–OMe	–H	465.08	−5.81	−7.44	−40.64	<30
13d		–OMe	–H	504.58	−6.90	−7.26	−63.40	90.64
13e	–H	–H	–F	381.37	−7.50	−6.36	−48.85	<30
13f		–H	–F	395.40	−7.22	−6.51	−48.22	<30
13g		–H	–F	471.50	−5.05	−7.42	−52.96	<30
13h		–H	–F	510.53	−7.88	−7.21	−60.23	89.15
13i	–H	–NO2	–H	390.39	−7.18	−6.97	−59.30	<30
13j		–NO2	–H	404.42	−4.52	−7.70	−53.11	<30
13k		–NO2	–H	480.51	−3.68	−6.27	−56.01	<30
13l		–NO 2	–H	519.55	−5.50	−7.09	−70.88	89.64
Control		Ex527				−7.78	−63.58	97.73

^aThe italicized rows represent the ligands chosen for further studies.