Carbonic anhydrase inhibitors. Inhibition of red blood cell ostrich (Struthio camelus) carbonic anhydrase with a series of aromatic and heterocyclic sulfonamides

Figures & data

Table I.  Kinetic parameters for CO₂-hydration reaction catalysed by the cytosolic α-CA isozymes of mammalian and avian origin and their susceptibility to acetazolamide inhibition.

Isozyme	Activity level	kcat (s^− 1)	kcat/Km (M^− 1·s^− 1)	KI (acetazolamide) (nM)
hCA I*	moderate	2·10^5	5·10^7	250
hCA II*	very high	1.4·10^6	1.5·10^8	12
hCA III**	low	1.0·10^4	3.10^5	300,000
mCA XIII*	moderate	8.3·10^4	4.3·10^7	17
ScCA	high	1.2·10^6	1.8·10^7	303

h = human; m = murine; sc = ostrich isozymes. * From refs. [25,32]; ** From ref. [3].

Table II.  hCA I, II and scCA inhibition data with sulfonamides 1–5, acetazolamide (AZA), ethoxzolamide (EZA) and sulfanilamide (SA). Data for hCA I and II are from refs. 2439-44.

			KI (nM) *
No	n	R	hCA I^a	hCA II^a	scCA^b
1a	0	CH3CO	21400	246	4550
1b	0	CF3CO	14600	133	4700
1c	0	EtCO	19700	232	3600
1d	0	n-PrCO	19300	227	397
1e	0	i-PrCO	23500	258	573
1f	0	n-BuCO	17650	214	260
1g	0	t-BuCO	20600	230	540
1h	0	PhCO	3300	37	3245
1i	0	MeSO2	125	64	66
1j	0	PhSO2	103	49	2430
1k	0	4-AcNHC6H4SO2	245	82	2600
1m	1	PhSO2	81	40	318
1n	1	PhNH–C( = S)	266	12	2970
1p	2	PhNH–C( = S)	50	53	2980
1q	2	PhNH–C( = O)	430	75	39
1r	2	4-H2NO2SC6H4NH–C( = S)	37	4	3030
1s	2	4-H2NO2SC6H4CO	40	5	25
2	–	PhNH–C( = O)	1500	150	3650
3	–	PhNH–C( = O)	900	100	69
4a	–	4-BrC6H4SO2	3	2	62
4b	–	4-O2NC6H4SO2	3	1	72
5	–	Furan-2-yl-CO	290	6	768
AZA	–	–	250	12	303
EZA	–	–	25	8	3.9
SA	–	–	28000	300	570

* Mean from three assays (errors in the range of 5–10% of the reported value).

^a Human, recombinant enzyme; ^b Struthio camelus red blood cell enzyme.

Vullo D, Voipio J, Innocenti A, Rivera C, Ranki H, Scozzafava A, Kaila K, Supuran T. Bioorg Med Chem Lett 2005; 15: 971–976

 PubMed Web of Science ®Google Scholar

Lehtonen J, Shen B, Vihinen M, Casini A, Scozzafava A, Supuran CT, Parkkila AK, Saarnio J, Kivela AJ, Waheed A, Sly WS, Parkkila S. J Biol Chem 2004; 279: 2719–2727

 PubMed Web of Science ®Google Scholar

Supuran CT. Carbonic anhydrase—Its inhibitors and activators, CT Supuran, A Scozzafava, J Conway. CRC Press, Boca Raton 2004; 1–23

 Google Scholar

Vullo D, Franchi M, Gallori E, Antel J, Scozzafava A, Supuran CT. J Med Chem 2004; 47: 1272–1279

 PubMed Web of Science ®Google Scholar