Synthetic Development of New 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanines under Microwave Irradiation and Their Effects on Tumor Cell Lines and against Protein Kinases

Abstract

Abstract:A new route to 3-(4-arylmethylamino)butyl-5-arylidene-2-thioxo-1,3-thiazolidine-4-one 9 was developed in six steps from commercial 1,4-diaminobutane 1 as starting material. The key step of this multi-step synthesis involved a solution phase "one-pot OPEN ACCESSMolecules 2015, 20 12413 two-steps" approach assisted by microwave dielectric from N-(arylmethyl)butane-1,4-diamine hydrochloride 6a-f (as source of the first point diversity) and commercial bis-(carboxymethyl)-trithiocarbonate reagent 7 for construction of the rhodanine platform. This platform was immediately functionalized by Knoevenagel condensation under microwave irradiation with a series of aromatic aldehydes 3 as second point of diversity. These new compounds were prepared in moderate to good yields and the fourteen synthetic products 9a-n have been obtained with a Z-geometry about their exocyclic double bond. These new 5-arylidene rhodanines derivatives 9a-n were tested for their kinase inhibitory potencies against four protein kinases: Human cyclin-dependent kinase 5-p25, HsCDK5-p25; porcine Glycogen Synthase Kinase-3, GSK-3α/β; porcine Casein Kinase 1, SsCK1 and human HsHaspin. They have also been evaluated for their in vitro inhibition of cell proliferation (HuH7 D12, Caco 2, MDA-MB 231, HCT 116, PC3, NCI-H727, HaCat and fibroblasts). Among of all these compounds, 9j presented selective micromolar inhibition activity on SsCK1 and 9i exhibited antitumor activities in the HuH7 D12, MDA-MBD231 cell lines.

Anticancer Profile of Rhodanines: Structure–Activity Relationship (SAR) and Molecular Targets—A Review

“…In turn, structure 37 turned out to be more active against HL-60 cells, with an inhibitory value of almost 60%. Based on the presented data, Novel 3-(4-Arylmethylamino)butyl-5-arylidene-rhodanine, 35, was synthesized [40], and its antitumor activity was tested. This structure exhibited promising antitumor effects in the HuH7 D12, HaCat, and MDA-MBD 231 cell lines, with IC 50 values below 10 µM (Figure 18).…”

Synthesis of bioactive quinazolin-4(3H)-one derivatives via microwave activation tailored by phase-transfer catalysis

“…Searching for new synthetic methodologies of 2,3-disubstituted quinazolin-4(3H)-ones in order to improve their synthetic medicinal applications are in demand. Accordingly, uses of ultrasonic, microwaves, solvent-free conditions, as well as ionic catalysts and phase-transfer catalysis are modern attractive synthetic approaches which were successfully applied for heterocycles synthesis, quinazolin-4(3H)-ones in particular (11). No one can deny that MW technique is announced as a green approach characterized as clean, simple, efficient and environment-friendly technique.…”

A practical multi-step synthesis of ethyl N-functionalized $$\varvec{\upbeta }$$ β -amino benzimidazole acrylate derivatives as promising cytotoxic agents

“…at 90°C we obtained desired arylaldimines 9(a-p) (68-98% yields, Table 1). Next, transforming arylaldimines 9(a-p) into mono N-protected diamines 10(a-p) was accomplished with 5 equivalents of NaBH 4 in MeOH at 50 °C for 24 h [17]. Compounds 10(a-p) were obtained as crystallized or viscous products in yields ranging from 73 to 98%.…”