In vitro activity of sulfonamides against red cell carbonic anhydrases

The activity of 28 sulfonamides against dog red cell carbonic anhydrase was ... centration upon enzyme activity, and upon the drug-enzyme interaction,...
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CARBOSIC ANHYDRASE INHIBITION

AIarch 1968

229

TABLE I 160

( X 10')

OF

-

SGLFONAMIDESAGAINST CRUDE DOGRBC CARBONIC ANHYDRASE AT 0.3'u

---SEI-

Class and coinpd

Carbonate

Barbital R R

A. Bcnzenesulfouamides: R . 0 5 0 / / It 2

Time, min

__-__

EI-

_ I -

Carbonate

Barbital

Time, min

...

4 2 2 2 Ne 2

hH-

R3

H H

19 5 113 34 40 28

H CHICONH CHI H H NHz

H KH2

H H

...

Se 2 2 Ne Ne Ne

13

... ... ... 57

2 0.2 2.0 2.7 1.3 6.0

0.2

... ... ...

4.0

B. Aliphatic Sulfouamides: RCI-IISO,XH~

...

3000 7200 600

C.

Benzothiazole Sulfonamides:

...

...

?I000 7200 300

15 10

...

...

*.. ... ...

2 2 2

Ra:,=/C-SO:h.Hr

...

0.04 0.04

OCzHb (ethoxzolamide)

Ne Ne Se

0.03

0.01

.

I

.

...

0.02

2

...

S-1

D. Thiadiazole Sulfonamides: R-$,

,{-SO,NH, S

R

NH2 CHICOXH (acetazolamide) CeHjSOzNH ( I ) p-NH&e,H$02NH o-ClCBH4 (11)

0.6 0.2 0.03 0.04 0.03

...

0.03

2 2 2 2 1

CH,N-S I ll CH,CON=C, ,C--SO?NH$

0.17

0.12

0.03

0.02

2 2 2 2 2

2

0.07

0.07

5

E. Disulfonamides (Saluretics) and Congeners lJ3-Disulfamylbenzene 21 ... Se 1,4-Disulfamylbenzene 14 ... Ne 1,3-Disulfamyl-4,5-dichlorobenzene(dichlorphenamide) 0.7 0.7 10 5-Chloro-2,4-disulfamylaniline (salamid) 22 ... 5

0.08 0.06 0.03

...

2 2 2

(methazolamide)

S

(chlorothiazide)

II 0

...

...

0.02 0.023

...

... 0.03

...

..

14

5

0.07

0.06

5

(hydrochlorothiazide)

225

240

10

1.8

1.2

3

(flumethiazide)

123

...

Se

4

...

2

350

...

2

0.2

...

2

2

0.03

0.03

20

Ke

0.1

...

...

9

...

2

c1 *C-cH.SCH H-XSO a y , Aso. H

a

(benzthiazide)

(chlorthalidone)

&Qc, C'NH

...

0.03 0.02

18

(trichlormethiazide)

'

0.2 0.03

14

2

16

...

SOJH,

F. Quaternary Ammonium Sulfonamide 300

...

2

Procedure is given in ref 2 and Methods section. The time given is the minimum needed for equilibration. The enzyme used was 0.25 ml of a 1: 100 suspension of whole dog blood in water. This is approximately 5 X to 2 enzyme units in the carbonate system and 5 in barbital.2' (L

S e means