Synthesis of pro-apoptotic indapamide derivatives as anticancer agents

Abstract

benzamide 12 demonstrated the highest proapoptotic activity among all synthesized compounds on melanoma cell lines MDA-MB-435 with 3.7% growth inhibition at the concentration of 10 mM. Compound 12 (SGK 266) was evaluated in vitro using the MTT colorimetric method against melanoma cancer cell line MDA-MB435 growth inhibition for different doses and exhibited anticancer activity with IC 50 values of 85-95 mM against melanoma cancer cell line MDA-MB435. In addition, this compound was investigated as inhibitors of four physiologically relevant human carbonic anhydrase isoforms, hCA I, II, IX and XII. The compund inhibited these enzymes with IC 50 values ranging between 0.72 and 1.60 mM.

Inhibitory activity against carbonic anhydrase IX and XII as a candidate selection criterion in the development of new anticancer agents

“…Disappointingly, a large fraction of publications on the subject reported compounds' cytotoxicity data obtained in normoxic conditions thus making the involvement of hCA IX and XII debateable [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] . Although such testing can be relevant in some cases, we consider these conditions irrelevant as long as antiproliferative activity of hCA inhibitors is concerned.…”

“…Understanding the significance of the candidate molecule prioritisation problem in question is essential while ignoring it may lead to many promising compounds being overlooked in want of more potent hCA IX/XII inhibitors. Aiming to draw a more informative picture, we have graphically represented the relationship between the anticancer effect (in this case, irrespective of the specific experimental conditions employed in various studies) and the hCA IX/XII inhibitory activity of the compounds [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][49][50][51][52][53][54][55][56][57][58][71][72][73][74] . In order to summarise the somewhat heterogeneous literature data, we have visualised the reported antiproliferative agents in the plots with the Y-axis displaying K i 's against hCA IX (Figures S1 and S2) and hCA XII ( Figures S3 and S4).…”

Synthesis and bioactivity studies of 1-aryl-3-(2-hydroxyethylthio)-1-propanones

“…The 1-aryl-3-(2-hydroxyethylthio)-1-propanone investigated here showed rather low tumor-specificity although they induced apoptosis, suggesting that apoptosis-inducing activity itself does not guarantee the antitumor effects. Chemical modifications of the best compound detected here, EU9, are thus necessary to further evaluate such derivatives for their biological activity, as cytotoxic agents or CA inhibitors [40][41][42][43] . …”

Development of Thiazolidinones as Fungal Carbonic Anhydrase Inhibitors

“…sulfonamides and their bioisosteres, carboxylates and their derivatives, phenols, and so on). Thiazolidinones were recently assayed as potent antifungal agents [39,40], and some of them were tested as carbonic anhydrase inhibitors in order to discover and develop innovative mechanisms of inhibition [37,41]. From the data reported in Table 2, it is possible to extrapolate a very remarkable selectivity profile of our thiazolidinones against this fungal β-CA over the two ubiquitous human isoforms (hCA I and II) being the selectivity index (SI) for compound 4h > 1000 (expressed as the ratio between K I CA I or II and K I CgNce103 values) and >100 for most of the other compounds.…”