Sulphonamides incorporating 1,3,5-triazine structural motifs show antioxidant, acetylcholinesterase, butyrylcholinesterase, and tyrosinase inhibitory profile

Figures & data

Scheme 1. General synthetic route for the synthesis of benzenesulfonamides incorporating 1,3,5-triazine moieties. Reagents and conditions: (i) R₁ (–4 F, –4MeO, –3,4diCl, and –3NO₂), DMF, 0 to 5 °C, 1 h, then 30–40 °C, 8 h, (ii) R₂H (dimethylamine, morpholine and piperidine), DMF, room temperature, 1 h, then 90 °C, 5 h.

Table 1. Antioxidant activity of sulphonamides 2 and 3.

			IC50 (µM)^a
			DPPH free radical	ABTS cation radical	Metal chelating
Comp.	R1	R2	Scavenging activity	Scavenging activity	Activity
2a	–4F	Cl	469.75 ± 1.17	>1000	488.29 ± 0.84
2b	–4MeO	Cl	500.97 ± 1.17	>1000	164.26 ± 0.68
2c	–3,4diCl	Cl	304.52 ± 1.38	>1000	109.63 ± 0.80
2d	–3NO2	Cl	443.26 ± 1.38	>1000	296.78 ± 0.52
3a	–4F	–N(Me)2	>1000	>1000	84.98 ± 1.14
3b	–4F		73.25 ± 0.52	>1000	148.03 ± 0.61
3c	–4F		>1000	>1000	338.90 ± 0.59
3d	–4MeO	–N(Me)2	102.65 ± 1.17	294.12 ± 1.20	337.51 ± 0.55
3e	–4MeO		>1000	>1000	84.32 ± 0.39
3f	–4MeO		>1000	408.44 ± 1.67	98.84 ± 0.90
3g	–3,4diCl	–N(Me)2	609.35 ± 0.98	>1000	139.15 ± 1.15
3h	–3,4diCl		60.18 ± 0.59	>1000	147.60 ± 0.82
3i	–3,4diCl		351.97 ± 1.33	>1000	99.10 ± 0.52
3j	–3NO2	–N(Me)2	58.59 ± 0.12	>1000	98.84 ± 0.90
3k	–3NO2		336.28 ± 1.43	481.21 ± 0.97	88.42 ± 0.75
3l	–3NO2		114.38 ± 0.60	>1000	115.46 ± 0.87
BHA^b	–	–	61.72 ± 0.85	45.40 ± 1.08	–
BHT^b	–	–	232.11 ± 3.01	26.54 ± 0.18	–
α-Tocopherol^b	–	–	56.86 ± 0.77	34.12 ± 0.41	–
EDTA^b	–	–	–	–	52.35 ± 1.15

^a IC₅₀ values represent the means (standard deviation of three parallel measurements (p < 0.05).

^b Reference compounds.

Table 2. Anti-cholinesterase and anti-tyrosinase activity of compounds 2 and 3.

			Anticholinesterase activity^a
Comp.	R1	R2	AChE assay	BChE assay	Tyrosinase activity^a
2a	–4F	Cl	NA	77.41 ± 1.19	38.96 ± 0.12
2b	–4MeO	Cl	96.37 ± 1.71	91.99 ± 0.60	14.21 ± 0.40
2c	–3,4diCl	Cl	NA	87.44 ± 1.46	33.44 ± 0.82
2d	–3NO2	Cl	22.38 ± 1.09	91.40 ± 1.48	NA
3a	–4F	–N(Me)2	NA	34.67 ± 0.83	13.50 ± 0.04
3b	–4F		14.18 ± 0.41	88.76 ± 0.97	15.34 ± 0.87
3c	–4F		36.55 ± 1.17	89.21 ± 1.75	6.29 ± 0.39
3d	–4MeO	–N(Me)2	91.10 ± 1.42	96.94 ± 1.61	27.76 ± 0.22
3e	–4MeO		NA	NA	30.37 ± 0.17
3f	–4MeO		NA	95.14 ± 1.17	86.35 ± 1.39
3g	–3,4diCl	–N(Me)2	NA	10.23 ± 0.70	58.49 ± 0.86
3h	–3,4diCl		93.19 ± 2.33	98.50 ± 1.63	24.13 ± 0.52
3i	–3,4diCl		NA	88.48 ± 1.29	23.21 ± 0.97
3j	–3NO2	–N(Me)2	NA	92.14 ± 1.02	77.30 ± 1.42
	–3NO2		28.42 ± 0.76	65.44 ± 1.19	18.40 ± 0.43
3l	–3NO2		NA	94.94 ± 0.24	58.59 ± 0.89
Galantamine^b		–	84.20 ± 0.74	87.86 ± 0.24	–
Kojic Acid^b		–	–	–	95.26 ± 0.23

^a % inhibition values at 200 µM.

^b Standard drugs. NA: not active.