Sulfocoumarins as dual inhibitors of human carbonic anhydrase isoforms IX/XII and of human thioredoxin reductase

Figures & data

Figure 1. Sulfocoumarins 1 and their CA inhibition mechanism, the previously reported Ugi Michael acceptor TrxR inhibitors (fragments originating from the four components of the Ugi reaction are colour-coded) and the hypothesis for dual CA/TrxR targeting verified in this work.

Scheme 1. Synthesis of compounds 1a–d.

Table 1. Inhibitory profile towards four hCA isoforms, TrxR activity in SHSY5Y cell lysate and cytotoxicity towards cancer cell lines determined for compounds 1a–d (nd: not determined).

Compound	IC50, μM			TrxR IC50, μM	Ki, nM
	HT-1080	SHSY5Y	MCF-7		hCA I	hCA II	hCA IX	hCA XII
1a	11.0	22.0	1.8	154	>10,000	>10,000	7.8	17.7
1b	8.7	29.0	79.0	40	>10,000	>10,000	8.3	7.8
1c	12.3	18.4	101	156	>10,000	>10,000	8.5	7.1
1d	7.9	18.5	50.0	125	>10,000	>10,000	6.9	5.4
AAZ	nd	nd	nd	nd	250	12	25	5.7