Inhibition of bacterial α-, β- and γ-class carbonic anhydrases with selenazoles incorporating benzenesulfonamide moieties

Figures & data

Figure 1 Proposed role of CAs in Gram-negative bacteria. The α-CAs convert the diffused CO₂ inside the periplasmic space into bicarbonate, whereas the cytosolic β-and γ-CAs are responsible for the supplementation of CO₂ and bicarbonate for the cellular metabolism. Furthermore, all these enzymes play an important role in the cellular pH homeostasis¹.

Scheme 1 Synthesis of functionalized selenazoles 4a–f and 5a–c.

Scheme 2 Synthesis of substituted 2,5-selenazoles 8–11.

Table 1. Inhibition data against bacterial enzyme hpCAα, VchCAα, VchCAβ, VchCAγ, BpsCAβ and BpsCAγ of derivates 4–5, 8–11 and acetazolamide AAZ by a stopped-flow CO₂ hydrase assay²².

	KI (µM)a
Compound	hpCAα	VchCAα	VchCAβ	VchCAγ	BpsCAβ	BpsCAγ
4a	1.95	0.22	2.61	8.23	0.58	0.82
4b	2.11	0.85	6.54	4.11	0.80	0.91
4c	0.79	0.57	9.08	8.07	0.43	0.83
4d	2.03	0.71	8.60	5.72	0.65	0.67
4e	2.21	0.82	8.89	8.52	0.68	0.80
4f	1.73	0.92	8.40	5.83	0.62	4.39
5a	2.11	0.58	5.88	8.28	0.55	3.98
5b	1.64	0.27	8.95	9.29	0.36	7.00
5c	1.63	0.21	7.75	3.64	0.33	3.79
8	2.71	0.93	6.42	6.80	4.60	6.80
9a	2.72	0.94	7.70	8.90	0.92	8.90
9b	2.42	0.47	7.72	7.60	0.32	7.60
9c	2.84	0.77	9.08	6.23	5.50	6.23
10a	2.43	0.87	8.84	4.70	0.09	4.70
10b	2.43	0.46	8.59	8.74	4.69	8.74
10c	2.80	0.92	6.79	7.00	6.20	0.70
11	2.04	0.44	9.12	6.05	0.64	6.55
AAZ	0.02	0.007	0.45	0.47	0.74	0.15

^aMean from three different assays, by a stopped-flow technique (errors were in the range of ±5–10% of the reported values).

(a) Supuran CT. Carbonic anhydrase inhibitors and their potential in a range of therapeutic areas. Expert Opin Ther Pat 2018;28:709–12. (b) Supuran CT. Applications of carbonic anhydrases inhibitors in renal and central nervous system diseases. Expert Opin Ther Pat 2018;28:713–21. (c) Nocentini A, Supuran CT. Carbonic anhydrase inhibitors as antitumor/antimetastatic agents: a patent review (2008–2018). Expert Opin Ther Pat 2018;28:729–40. (d) Supuran CT, Capasso C. Biomedical applications of prokaryotic carbonic anhydrases. Expert Opin Ther Pat 2018;28:745–54.

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