Inhibition of the β-carbonic anhydrase from the dandruff-producing fungus Malassezia globosa with monothiocarbamates

Figures & data

Table 1. hCA I, II and MgCA inhibition data with MTCs 1−15, trithiocarbonate 16 and xanthate 17 by a stopped-flow CO₂ hydrase assay⁶³.

			KI^a
No.	R	R1	hCA I (nM)	hCA II(nM)	MgCA (µM)
1^b	H		891	26.7	14.1
2^b	H		>2000	43.7	18.9
3^b	H		>2000	35.0	7.81
4^b	n-Pr	n-Pr	>2000	46.7	1.85
5^b	n-Bu	n-Bu	909	>2000	7.52
6^b	i-Bu	i-Bu	681	43.0	8.61
7^b	Et	n-Bu	700	>2000	5.26
8^b	Me		827	44.5	9.16
9^b	Me	Bn	>2000	>2000	7.61
10^b	–(CH2CH2)–O–(CH2CH2)–		569	>2000	7.65
11^b	–(CH2CH2)–NH–(CH2CH2)–		876	22.4	7.41
12^b	–(CH2CH2)–N(4–F–C6H4)–(CH2CH2)–		895	46.8	8.33
13^b	–(CH2CH2)–N(4–CF3–C6H4)–(CH2CH2)–		>2000	43.6	4.22
14^b	–(CH2CH2)–N(3–Cl–C6H4)–(CH2CH2)–		686	>2000	15.9
15^b	–(CH2CH2)–N(CH2CONHC6H11)–(CH2CH2)–		949	45.9	6.13
16^b	Bn	–	4.1	0.70	8.12
17^b		–	64.1	5.4	16.2
AAZ			250	12	74

^a Mean from three different assays, by a stopped flow technique (errors were in the range of ±5–10% of the reported values); ^bhCA I and hCA II data from Ref.^14f.

Figure 1. (a) ESP atomic charges of 2 derived from a B3LYP/6–31 G*⁺. Red colour represents negative values of the electrostatic potential (b) Schematic representation of the binding mode of MTCs into the MgCA active site.

Figure 2. Docked orientations of compounds 2 and 9 (a); 8 (b) and 10 (c) within MgCA active site. Monomer A and B are coloured blue and green, respectively.

Khalifah RG. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. J Biol Chem 1971;246:2561–73.

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