Structure of Scheme 1 compounds with their elemental property, docking score, MM-GBSA binding energy and enzyme-based inhibition activity. The biological evaluation of enzyme-based inhibitory activity of test compounds at 10.0 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)
7a		–OMe	–H	421	−9.23	−6.26	−58.96	88.03
7b		–OMe	–H	450	−7.98	−7.06	−59.49	88.18
7c		–OMe	–H	464	−9.15	−6.68	−58.85	86.34
7d		–OMe	–H	537	−8.81	−6.70	−72.08	89.99
7e		–F	–H	409	−11.47	−6.51	−54.45	<30
7f		–F	–H	437	−9.32	−7.40	−54.66	<30
7g		–F	–H	451	−8.76	−6.08	−58.20	80.82
7h		–F	–H	525	−8.67	−5.84	−61.60	86.83
7i		–H	–Cl/F	472	−10.70	−7.08	−49.04	<30
7j		–H	–Cl/F	486	−9.71	−5.33	−33.49	<30
7k		–H	–Cl/F	559	−8.49	−5.61	−52.97	<30
7l		–H	–Cl/F	559	−8.12	−6.61	−56.97	<30
Control		Ex527				−7.78	−63.58	97.73

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