Three-component synthesis and carbonic anhydrase inhibitory properties of novel octahydroacridines incorporating sulfaguanidine scaffold

Figures & data

Scheme 1. Synthesis of acridine sulphaguanidine derivative compounds (4–18).

Table 1. Summary of purification procedure for hCA I and hCA II.

Purification steps		Activity (EU/mL)	Total volume (mL)	Protein (mg/mL)	Total protein (mg)	Total activity (EU)	Specific activity (EU/mg protein)	Yield (%)	Purification factor
Hemolysate		154.30	30.00	12.13	363.90	4629.00	12.72	100.00	1.00
Sepharose®4B-L-tyrosine  sulfanyl-amide	hCA I	456.20	5.00	0.43	2.15	2281.00	1060.90	49.27	83.40
affinity chromatography	hCA II	734.10	5.00	0.22	1.10	3670.50	3336.80	79.29	262.32

Figure 1. Inhibition percentages of 4–18 on hCA I and hCA II isoenzymes, as graphical presentation.

Figure 2. Percent enzyme activity versus inhibitor concentration graphics of the inhibitory compounds. (a) Effect of 7 on the esterase activity of hCA II. (b) Effect of 8 on the esterase activity of hCA I.

Table 2. Inhibition percentages and IC₅₀ values of synthesized compounds on hCA I and hCA II isoenzymes.

		IC50^b^,^c Values (μM)			Inhibition (%)^a^,^b^,^c
Inhibitor	Ar-	hCA I	hCA II	hCA I	A	hCA II	B	hCA II/hCA I
AAZ	–	0.418 ± 0.008	0.306 ± 0.004	95.74 ± 0.95	–	98.02 ± 0.96	–	1.02
4	-C6H5	179.4 ± 3.0	217.8 ± 2.0	62.50 ± 0.63	–	54.21 ± 0.55	–	0.87
5	4-CN-C6H4	204.8 ± 6.1	114.3 ± 3.1	58.47 ± 0.59	1.07	68.75 ± 0.69	0.79	1.18
6	3-CN-C6H4	–	–	35.01 ± 0.35	1.79	32.14 ± 0.32	1.69	0.92
7	4-NO2-C6H4	145.7 ± 4.2	86.7 ± 3.0	57.01 ± 0.57	1.10	69.33 ± 0.71	0.78	1.22
8	3-NO2-C6H4	118.4 ± 7.0	153.8 ± 5.2	73.91 ± 0.73	0.85	57.58 ± 0.56	0.94	0.78
9	4-F-C6H4	–	–	24.19 ± 0.25	2.58	20.45 ± 0.21	2.65	0.85
10	4-Cl-C6H4	187.6 ± 10.1	138.2 ± 4.3	54.29 ± 0.54	1.15	76.47 ± 0.77	0.71	1.41
11	4-Br-C6H4	123.1 ± 3.1	159.8 ± 2.1	72.97 ± 0.73	0.86	60.57 ± 0.61	0.89	0.83
12	2,4-Cl2-C6H3	–	–	28.74 ± 0.29	2.17	27.56 ± 0.26	1.97	0.95
13	4-OCH3-C6H4	257.5 ± 5.2	177.3 ± 2.2	50.13 ± 0.51	1.25	61.11 ± 0.61	0.89	1.22
14	2,4-(OCH3)2-C6H3	–	–	22.17 ± 0.22	2.82	21.14 ± 0.20	2.56	0.95
15	4-OH-C6H4	–	–	30.78 ± 0.31	2.03	29.99 ± 0.30	1.81	0.97
16	4-CH3-C6H4	160.6 ± 1.0	249.4 ± 10.2	71.05 ± 0.70	0.88	50.87 ± 0.51	1.07	0.72
17	4-CH3CH2-C6H4	231.3 ± 5.0	219.8 ± 3.0	57.35 ± 0.57	1.09	58.00 ± 0.58	0.93	1.01
18	4-Biphenyl	–	–	34.44 ± 0.34	1.81	35.66 ± 0.36	1.52	1.04

AAZ was used as control compound.

^a 0.1% inhibitor concentration was used in the esterase activity assays.

^b Mean ± standard error, from three different assays.

^c p < 0.0001 for all analysis.

A values were calculated by dividing the inhibition percentage value of the Compound 4 against hCA I to inhibition percentage value of (5–18) against hCA I.

B values were calculated by dividing the inhibition percentage value of the Compound 4 against hCA II to inhibition percentage value of (5–18) against hCA II.