A series of novel sulfonamide derivatives bearing pyrrole and pyrrolopyrimidine scaffolds were synthesized and screened as carbonic anhydrase inhibitors. The inhibition activity of the synthesized compounds was evaluated against the cytosolic human carbonic anhydrase isoforms I and II and the transmembranal isoforms IX and XII. Several candidates showed potent inhibitory activity against IX and XII isoforms. Furthermore, ex vivo screening of cytotoxic selectivity and activity of the most potent derivatives were carried out against normal cells (WI38) and cervical cancer cell line (HeLa) under normal and hypoxic conditions using acetazolamide as reference drug. Compound 11b potency was nearly three folds higher in hypoxic than normoxic condition whereas that of compound 11f was nearly four folds higher in hypoxic vs. normoxic HeLa cells. All the screened derivatives exhibited less potency on normal cells (WI38). Molecular docking was carried out to discover the possible binding mode of compounds within the active site of isoform CA IX.

中文翻译：

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吡咯烷和吡咯并嘧啶磺酰胺通过抑制跨膜碳酸酐酶而在缺氧中充当细胞毒剂。

合成了一系列带有吡咯和吡咯并嘧啶骨架的新型磺酰胺衍生物，并筛选了它们作为碳酸酐酶抑制剂。评价了合成化合物对胞质人碳酸酐酶同工型I和II以及跨膜同工型IX和XII的抑制活性。几个候选物显示出对IX和XII同工型的有效抑制活性。此外，使用乙酰唑胺作为参比药物，在正常和低氧条件下对正常细胞（WI38）和宫颈癌细胞系（HeLa）进行了离体筛选，对最强衍生物的细胞毒性选择性和活性进行了研究。在低氧条件下，化合物11b的效力比在高氧条件下高近三倍，而在低氧条件下，化合物11f的效力比在高氧条件下高出近四倍。所有筛选的衍生物对正常细胞（WI38）均显示出较低的效价。进行了分子对接，以发现化合物在同工型CA IX活性位点内的可能结合方式。