Carbonic anhydrase inhibitors. Biphenylsulfonamides with inhibitory action towards the transmembrane, tumor-associated isozymes IX possess cytotoxic activity against human colon, lung and breast cancer cell lines

Figures & data

Table I.  Elemental analysis data for the new compounds11–14 reported here.

No	Mp (°C)	Yield (%)	Elem anal. (calc,/found)
			% C	% H	%N	%S
11	>300	75	46.30/46.27	3.53/3.50	9.00/8.96	20.57/20.52
12	168	80	49.55/49.36	4.39/4.42	8.25/8.29	18.87/18.90
13	>300	85	33.92/33.88	2.59/2.40	9.89/9.50	22.61/22.51
14	>300	67	27.00/26.91	2.25/2.03	15.75/15.50	27.00/26.85

Table II.  FTIR spectroscopy of 4,4′ biphenyl disulphonamide derivatives11–14.

No	Ar (CH)	SO2	NH	NH2	CH2
		cm^− 1
11	3053	1140, 1330	3250	3359, 3390	–
12	3060	1150, 1330	3276	3290, 3385	2790
13	3082	1142, 1315	3248	3277, 3374	–
14	3058	1187,1342	3255	3270,3394	–

Scheme 1.  Preparation of biphenylsufonamides11–14.

Table III.  CA inhibition data of sulfonamides11–14 reported in the present paper and standard inhibitors 1 - 8, against isozymes I, II (cytosolic), IX and XII (transmembrane), by a stopped-flow, CO₂ hydration assay [28].

Inhibitor	hCA I^a	KI^* hCA II^a	hCA IX^b	hCA XII^b
	(nM)	(nM)	(nM)	(nM)
1	250	12	25	5.7
2	50	14	27	3.4
3	25	8	34	22
4	1200	38	50	50
5	50000	9	52	3.5
6	45000	3	37	3.0
7	31	15	24	3.4
8	3450	21	34	12
11	675	64	59	145
12	604	43	23	213
13	1237	129	79	362
14	693	21	35	154

*Errors in the range of 5–10% of the shown data, from three different assays, by a CO₂ hydration stopped-flow assay [28]

^aHuman, recombinant isozymes,

^bCatalytic domain of human, cloned isoform [12,13].

Figure 1.  Inhibition of growth of three tumor cell lines (human colon cancer cell line HCT116, human lung cancer cell line H460 and human breast cancer cell line MCF-7) with compounds11 (A), 12 (B), 13 (C) and 14 (D).

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