(3,4-Dihydroxyphenyl)(2,3,4-trihydroxyphenyl)methanone and its derivatives as carbonic anhydrase isoenzymes inhibitors

Figures & data

Scheme 1.  Reagents and conditions. (a) LiBr (1.1 equiv.)/CAN (1.1 equiv.), CH₃CN, RT, 3 d, 97%; (b) LiBr (6.0 equiv.)/CAN (6.0 equiv.), CH₃CN, RT, 6 d, 95%; (c) KOH-NH₂NH₂/(OHCH₂)₂, 110°C–190°C, 3 d, 83%; (d) LiBr (2.1 equiv.)/CAN (2.1 equiv.), CH₃CN, RT, 3 d, 95%; (e) LiBr (1.1 equiv.)/CAN (1.1 equiv.), CH₃CN, RT, 3 d; (f) BBr₃, CH₂Cl₂, 96%.

Table 1.  Summary of purification procedure for human carbonic anhydrase isoenzymes (hCA I and hCA II) by a sepharose-4B-thyrosine-sulfanilamide affinity column chromatography.

Purification steps		Activity (EU/mL)	Total volume (mL)	Protein (mg/mL)	Total protein (mg)	Total activity (EU)	Specific activity (EU/mg)	Yield (%)	Purification factor
Hemolysate		125	30	16.28	488.4	3750	7.68	100	1
Sepharose-4B- thyrosine-sulfanilamide affinity column chromatography	hCA I	258	8	0.34	2.04	2064	758.82	55.04	98.80
	hCA II	600	4	0.14	0.56	2400	4285.71	64.00	558.04

EU, enzyme unit.

Table 2.  Human carbonic anhydrase isonzymes (hCA I and hCA II) inhibition data with some synthesised bromophenols, by an esterase assay with 4-nitrophenylacetate as substrate.

Compounds	hCA-I		hCA-II		KI (mM)
	IC50 (μM)	r^2	IC50 (μM)	r^2	hCA-I	hCA-II
5	27.77	0.9925	142.01	0.8553	32.48 ± 13.74	23.03 ± 10.94
13	6.92	0.9327	18.52	0.8818	6.77 ± 0.87	3.25 ± 1.13
14	3.22	0.8986	24.47	0.9588	1.19 ± 1.4	28.56 ± 18.82
15	54.28	0.8608	79.42	0.8424	8.36 ± 1.21	42.48 ± 23.42
16	4.28	0.9411	63.64	0.9884	2.59 ± 1.45	118.41 ± 66.36