Inclusion of a 5-fluorouracil moiety in nitrogenous bases derivatives as human carbonic anhydrase IX and XII inhibitors produced a targeted action against MDA-MB-231 and T47D breast cancer cells

Benzylaminoethyureido-Tailed Benzenesulfonamides: Design, Synthesis, Kinetic and X-ray Investigations on Human Carbonic Anhydrases

“…8. General Procedure for the Synthesis of compound [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35]. A solution of 5a-b (0.2 g, 1.0 eq) in dry MeOH was treated with Et 3 N (1 eq) then the reaction mixture was cooled to 0 • C and benzaldehyde 6-15 (1 eq) was added.…”

“…The reaction was continued for 2 h at 0 • C, followed by addition of sodium borohydride (4 eq) and reaction continued until the consumption of starting materials (TLC monitoring). The solvents were removed under reduced pressure and the title compounds were either obtained from filtration of the precipitates formed after addition of 5-10 mL of ice-cold water, followed by washing with Et 2 O (3 × 5 mL) (21,26,33) or extracted from ethyl acetate. In the latter the combined organic layers were washed with H 2 O (3 × 20 mL), dried over Na 2 SO 4 , filtered and concentrated in vacuum to give a residue that was crystallized from EtOH-Water (1:1) (17,22,25,34) or purified by silica gel column chromatography by eluting with 10%MeOH in DCM as the mobile phase (16, 18-20, 23-24, 27-30, 35).…”

“…In this contest the "tail approach" proved to be the most successful strategy within the field of Medicinal Chemistry on targeting specific CA isoforms. Such an approach makes use of the interactions occurring between the chemical moieties inserted in the CAIs tails and the amino acid residues located at the rim of the enzymatic cavity, which have the lowest homology sequences among the CA isoforms of the α-class [17,[21][22][23][24][25][26][27]. An important structural consideration is the role of the linker connecting the tail and the warhead sections within CAI molecules in order to make use of the tail strategy.…”

Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation

“…Inspired by the aforementioned discoveries and in connection with our research work concerning the development of effective anti-breast cancer agents [15][16][17][18], we were endeavored to design novel indole derivatives that promisingly possess antiproliferative activity. Perceiving the significance of these facts and based on our growing research interest in marine natural products, we were persuaded to tackle this study to design and synthesize marine-inspired bis-indole derivatives that have potential in vitro antitumor activity against breast cancer.…”

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

“…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).…”