4β-[(4-Alkyl)-1,2,3-triazol-1-yl] podophyllotoxins as anticancer compounds: Design, synthesis and biological evaluation

Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings

“…The solvent was evaporated and the residue was purified by column chromatography to afford the cycloaddition product. (25) (27). White amorphous powder, yield 98% (after chromatography with CHCl 3 /CH 3 1'''), 72.1 (C-5'''), 71.3 (C-3'''), 71.3 (C-11), 69.8 (C-2'''), 68.9 (C-4'''), 63.9 (C-2), 62.9 (C-6''), 61.7 (C-6'''), 56.8 (3', 5'-OCH 3 ), 46.6 (C-4), 45.1 (C-1), 39.9 (C-3), 20 (29).…”

“…Typically, a terminal alkyne and an azide undergo a copper-catalyzed [3+2]-cycloaddition to generate a substituted 4β-triazole ring [25,26]. Podophyllotoxin derivatives containing the featured 4β-triazole ring have also been reported as potential DNA topoisomerase-II inhibitors [27], including a few compounds bearing a sugar residue [28]. Through click reactions we have now synthesized a series of glucose-podophyllotoxin conjugates in order to systematically study the effect of: (a) the length of the linker; (b) the substituent on the glucose; (c) the configuration of the anomeric carbon of glucose residue; and (d) the substituent on the 4-position of the E-ring of the podophyllotoxin scaffold on the anticancer activity of such conjugates.…”

A new route for the synthesis of pyrimido[2,1-b][1,3]thiazine ring system

“…The majority of the compounds proved to be more potent than etoposide in selected human cancer cell lines. [15] A library of 1,2,3-triazole analogs of combretastatin A-4 were prepared by Odlo et al, [16] and one of the triazole analogs displayed potent cytotoxic activity against several cancer cell lines with IC50 values in the nanomolar range. Recently we designed and synthesized a family of 1,2,3-triazole-tethered thienopyrimidines-monosaccharides.…”

Synthesis, characterization and biological evaluation of 7-substituted- 4-((1-aryl-1H-1,2,3-triazol-4-yl) methyl)-2H-benzo[b][1,4]oxazin- 3(4H)-ones as anticancer agents

“…Such compounds have also been reported as β3-selective adrenergic receptor agonists (Brockunier et al, 2000), kinase inhibitors (Olesen et al, 2003) and other enzyme inhibitors (Krasinski et al, 2005). In particular, by combining 1,2,3-triazoles with other pharmacophore via click chemistry, a number of compounds with potent biological active compounds were synthesized (Stefely et al, 2010;Reddy et al, 2011;Singh et al, 2012). 1,2,3-triazole moiety containing drug molecules such as tazobactam (Bennet et al, 1991), cefatrizine (Stilwell et al, 1975) and carboxyamidotriazole (Soltis et al, 1996) are available (Fig.…”