Application of hydrazino and hydrazido linkers to connect benzenesulfonamides with hydrophilic/phobic tails for targeting the middle region of human carbonic anhydrases active site: Selective inhibitors of hCA IX

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

“…To our delight, however, there is a large number of mechanistically relevant experiments reported in the literature which address the ability of hCA IX/XII inhibitors to block the growth of hypoxic cancer cells overexpressing the target isozymes [49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] . Moreover, a certain cohort of studies revealed compounds possessing both favourable hCA inhibitory profile and significant anticancer activity, as exemplified by structures 5-13 ( Figure 2) [49][50][51][52][53][54][55][56][58][59][60][61][64][65][66][67] . In fact, quite a number of single-digit nanomolar hCA IX/XII inhibitors significantly suppressed cancer cell growth.…”

“…Meanwhile, the drug-like character of some frontrunners makes them intriguing starting points for medicinal chemistry optimisation. Once selected based on their hCA inhibitory profiles, these compounds might be useful indeed in designing antineoplastic drugs either of combinative or single-agent use [49][50][51][52][53]55,56,61,65 .…”

“…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).…”

Computer-Aided Design, Synthesis, and Antiviral Evaluation of Novel Acrylamides as Potential Inhibitors of E3-E2-E1 Glycoproteins Complex from Chikungunya Virus

“…Finally, a total run-time of 5 min for each sample was allowed. These procedures are adaptations from works previously reported [ 107 , 108 , 109 ].…”

“…Finally, a total run-time of 5 min for each sample was allowed. These procedures are adaptations from works previously reported [107][108][109]. In general, an adaptation of methods described by Luo and collaborators (2015) was used [110], through a Knoevenagel condensation Doebner modification reaction [77].…”