Table 1.

Inhibition data of sulfonamides 1–15a–c and reference compound AAZ on hCAs I and II and VchCAs through the stopped-flow CO₂ hydrase assay.

Cpd	Scaffold	Series	R	KI (nM)					SI [$\frac{KI \mathit{hCA}\mathrm{ }\mathrm{I}}{KI\mathrm{ }\mathit{Vch}\mathrm{\alpha }\mathrm{CA}}$]	SI [$\frac{KI \mathit{hCA}\mathrm{ }\mathrm{II}}{KI \mathit{Vch}\alpha \mathrm{CA}}$]
				hCA Ia	hCA IIa	VchαCA	VchβCA	VchγCA
1	a	p-		25.4	7.2	78.1	18 300	n.a.	0.3	0.1
2	a	p-		9.7	3.1	43.1	16 800	39 900	0.2	0.1
3	a	p-		39.0	47.0	27.4	53 800	n.a.	1.4	1.7
4	a	p-		787	646	65.0	136 400	n.a.	12.1	9.9
5	a	p-		939	908	64.1	89 200	n.a.	14.7	14.2
6	a	p-		75.3	8.2	36.2	100 800	73 700	2.1	0.2
7	a	p-		87.0	31.4	37.0	19 000	69 800	2.4	0.9
8	a	p-		169	32.7	23.0	12 400	52 700	7.4	1.4
9	a	p-		538	82.2	78.8	115 000	n.a.	6.8	1.0
10	a	p-		896	338	7.5	12 500	92 900	119.5	45.0
11	a	m-		7.0	4.1	63.0	15 600	n.a.	0.1	0.1
12	a	m-		>1000	901	44.1	173 200	79 000	>22.7	20.4
13	a	m-		346	15.7	75.6	59 200	5600	4.6	0.2
14	a	m-		7.6	3.3	63.5	97 000	n.a.	0.1	0.1
15	a	m-		151	43.2	80.3	56 500	69 300	1.9	0.5
1	b	p-		62.6	3.2	53.0	17 700	49 400	1.2	0.1
2	b	p-		6.6	82.4	43.1	97 000	82 600	0.2	1.9
3	b	p-		16.7	6.0	66.0	116 400	86 900	0.3	0.1
4	b	p-		>1000	909	22.8	157 300	72 500	>43.9	39.9
5	b	p-		29.8	3.0	62.0	47 400	87 700	0.5	0.1
6	b	p-		18.4	4.8	79.0	51 400	93 100	0.2	0.1
7	b	p-		15.3	4.7	17.0	73 100	59 800	0.9	0.3
8	b	p-		26.5	5.0	61.4	53 200	n.a.	0.4	0.1
9	b	p-		160	8.4	78.6	141 400	n.a.	2.0	0.1
10	b	p-		92.0	26.6	36.2	4000	58 300	2.5	0.7
11	b	m-		443	35.5	59.4	132 500	n.a.	7.5	0.6
12	b	m-		86.4	8.2	73.1	120 800	9600	1.2	0.1
13	b	m-		269	32.4	75.5	70 400	n.a.	3.6	0.4
14	b	m-		20.3	86.0	72.3	16 000	72 400	0.3	1.9
15	b	m-		83.7	37.4	66.4	116 400	73 600	1.3	0.6
1	c	p-		54.4	4.3	7.1	134 000	5000	7.7	0.6
2	c	p-		16.1	3.7	27.0	83 600	3500	0.60	0.14
3	c	p-		194	46.3	47.0	106 000	50 200	4.1	1.0
4	c	p-		92.7	13.0	13.0	116 000	72 200	7.1	1.0
5	c	p-		6.2	3.4	47.2	n.a.	73 200	0.1	0.1
6	c	p-		7.8	3.1	9.7	108 000	82 800	0.8	0.3
7	c	p-		54.6	7.2	11.0	122 000	80 200	5.0	0.7
8	c	p-		8.0	3.1	2.6	127 200	8100	3.1	1.2
9	c	p-		604	423	4.7	113 100	54 900	128.4	90.0
10	c	p-		8.5	3.2	9.8	113 200	64 500	0.9	0.3
11	c	m-		60.6	31.1	50.3	100 200	6500	1.2	0.6
12	c	m-		462	500	11.0	n.a.	76 000	42.0	45.5
13	c	m-		30.3	84.1	4.0	121 800	73 700	7.6	21.0
14	c	m-		8.0	54.4	10.0	132 100	81 300	0.8	5.4
15	c	m-		36.3	8.0	47.0	122 000	8000	0.8	0.2
AAZ				250	12.1	6.8	451	473	36.8	1.8

K_I values are reported as means of three independent experiments by a stopped-flow technique. Errors are in the range of ± 5–10% of the reported values. Acetazolamide (AAZ) was used as a reference control in these assays. VchCAs are from V. cholerae species. Selectivity index (SI) values are calculated as indicated in the table. Compounds are presented based on the molecular scaffold (a, amine, b, amide, and c, urea) and the (meta- or para-) position with respect to the benzenesulfonamide core. n.a.: not active at 100 µM.

^aData from Ref. 40.