Structure–activity relationships for the interaction of 5,10-dihydroindeno[1,2-b]indole derivatives with human and bovine carbonic anhydrase isoforms I, II, III, IV and VI

Several 5,10-dihydroindeno[1,2-b]indole derivatives incorporating methoxy, hydroxyl, and halogen (F, Cl, and Br) moieties on the indene fragment of the molecule were prepared and tested against five carbonic anhydrase (CA, EC 4.2.1.1) isoforms. The inhibitory potencies of these compounds against the human (h) isoforms hCA I, II, IV, VI and bovine (b) isoform bCA III were assessed. Most of them exhibited low micromolar inhibition of these enzymes. KI values of these compounds against hCA I and hCA II were in the range of 2.14–16.32 μM, and 0.34–2.52 μM, respectively. Isozyme hCA IV was inhibited with KI-s in the range of 0.435–5.726 μM, while hCA VI with KI-s of 1.92–12.84 μM bCA III was inhibited with KI-s in the range of 2.13–17.83 μM. The structurally related compounds, 1,2-dimethoxybenzene, catechol and indole were also tested in order to understand the structure activity relationship. In silico docking studies of some derivatives within the active site of hCA I and II were also carried out in order to rationalize the inhibitory properties of these compounds and understand their inhibition mechanism.

CA inhibitory capacities of, 10-dihydroindeno[1,2-b]indole-based compounds (1–20) were reported. Some of the compounds, showed powerful inhibitory activities at low micromolar concentrations compared to well-known agents. This study may be useful for medicinal chemists to design new CA inhibitors with enhanced activity and other tailored properties which could be used in medical applications.Figure optionsDownload as PowerPoint slideHighlights
► Twenty 5,10-dihydroindeno[1,2-b]indole-based compounds were prepared.
► The compounds were tested against five members of carbonic anhydrase (CA).
► Some of the compounds showed good CA inhibition compared to the clinically used sulfonamides.
► In silico docking studies were also carried out and supported the kinetic assays.
► This study may assist to medicinal chemists to design new CA inhibitors with enhanced activity.