Novel thiazolone-benzenesulphonamide inhibitors of human and bacterial carbonic anhydrases

Figures & data

Figure 1. Selected example of FDA-approved sulphonamide carbonic anhydrase inhibitors.

Figure 2. (a) General structure of thiazolone-benzenesulphonamides as selective hCA IX inhibitors developed by Hassan ¹²; (b) General structure of thiazolone-benzenesulphonamides discussed in the paper.

Scheme 1. Reagents and conditions: (i) DMF, 25–40 °C, 15–48 h.

Figure 3. Representative tautomers of compounds 4.

Table 1. Inhibition data of human CA isoforms hCA I, II, and VII and bacterial β-CA isoforms MscCA, from Mammaliicoccus (Staphylococcus) sciuri, and StCA1 and StCA2, from Salmonella enterica (serovar Typhimurium) with compounds 4a–j in comparison with the standard sulphonamide inhibitor AAZ by a stopped flow CO₂ hydrase assay.

Compound	R	KI (nM)^a
		hCA I	hCA II	hCA VII	MscCAβ	StCA1	StCA2
4a	–H	63.9	3.4	1.4	786.6	82.4	275.2
4b	–CH3	31.5	4.3	0.9	481.4	89.9	538.1
4c	–CH2CH3	66.6	3.8	1.2	411.0	86.1	480.8
4d	–(CH2)2CH3	70.7	2.3	2.0	73.6	83.3	913.1
4e	–CH(CH3)2	85.4	7.3	7.5	701.3	81.1	866.9
4f	–(CH2)3CH3	75.0	3.2	6.2	2425.0	72.4	904.0
4g	–(CH2)5CH3	637.3	13.7	14.6	4026.3	83.6	4875.0
4h	–C6H5	90.4	1.3	7.3	1056.7	163.3	797.4
4i	–(CH2)2Br	74.6	2.2	2.1	924.5	69.2	515.1
4j	–F	137.5	3.7	1.9	848.7	90.9	955.9
AAZ	–	250	12.5	2.5	625	59	84

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

Nemr MT, AboulMagd AM, Hassan HM, Hamed AA, Hamed MI, Elsaadi MT. Design, synthesis and mechanistic study of new benzenesulfonamide derivatives as anticancer and antimicrobial agents via carbonic anhydrase IX inhibition. RSC Adv. 2021;11(42):26241–26257.

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