Synthesis of two phloroglucinol derivatives with cinnamyl moieties as inhibitors of the carbonic anhydrase isozymes I and II: an in vitro study

Figures & data

Figure 1. Chemical structures of phenolic compounds and synthesized compounds.

Scheme 1. Reagents and conditions: NaBH₄, EtOH, 0 °C, 30 min, 98%; (ii) PBr₃, diethylether, 0 °C, 1 h, 85%; (iii) Phloroglucinol (3), NaH, THF, rt, 17 h, 26%.

Figure 2. Polyacrylamide gel electrophoresis (PAGE) of the purified CA isozymes. Lane 1: standard proteins (62–16.5 kDa), lane 2: hCA I and lane 3: hCA II.

Table 1. Summary of the purification procedure for hCA I and hCA II.

Sample type	Total volume (ml)	Activity (EU/ml)	Protein (mg/ml)	Specific activity (EU/mg)	% Yield	Purification factor
Haemolysate	48.00	169.00	19.67	8.59	100.00	1.00
CA-I	9.60	498.00	0.57	873.70	58.90	101.70
CA-II	4.80	891.60	0.12	7430.00	52.7	864.95

Table 2. K_i values for the hCA I and hCA II inhibition data for compounds 1, 2, 4–10 and AZA by an esterase assay.

	Ki (μM)
Compounds	hCA I	hCA II
Phenol (1)	10.2*	5.5*
Pyrgallol (2)	7.41†	0.54†
p-Hydroxybenzoic (4)	1061‡	675‡
p-coumaric acid (5)	441‡	537‡
Ferulic acid (6)	408‡	210‡
Gallic acid (7)	1052‡	758‡
Syringic acid (8)	919‡	695‡
4-p-Methoxycinnamyl phloroglucinol (9)	77.00	88.92
4,6-bis-p-methoxycinnamyl  phloroglucinol (10)	n.d	83.22
Acetazolamide (AZA)	36§	3.7§

Mean from at least three determinations. Errors in the range of 3–5% of the reported value (data not shown).

* From Ref.^22–25

† From Ref.³

‡ From Ref.⁵

§ From Ref.¹⁵

Sarıkaya Oztürk SB, Toplal F, Sentürk M, et al In vitro inhibition of α-carbonic anhydrase isozymes by some phenolic compounds. Bioorg Med Chem Lett 2011;21:4259–62

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Sarıkaya Oztürk SB, Gülcin I, Supuran CT. Carbonic anhydrase inhibitors: inhibition of human erythrocyte isozymes I and II with a series of phenolic acids. Chem Biol Drug Des 2010;75:515–20

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Senturk M, Gulcin I, Dastan A, et al Carbonic anhydrase inhibitors. Inhibition of human erythrocyte isozymes I and II with a series of antioxidant phenols. Bioorg Med Chem 2009;17:3207–11

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