Synthesis of Novel Antiproliferative 1,2,3-triazole Hybrids Using the Molecular Hybridisation Approach

Abstract

A series of nine novel 1,2,3-triazole-chalcone derivatives were designed using the molecular hybridisation approach and synthesised by click chemistry. Most of the synthesised compounds exhibited moderate to good antiproliferative activity against oesophagus, gastric and neuroendocrine cancer cell lines, but a compound containing a p-bromo group in the A ring and a [(4,5-dihydrothiazol-2-yl)thio]methyl group attached at the 4-position of a p-[3-(1,2,3-triazol-1-yl)propyloxy] group in the B ring showed the highest activity with an IC50 value of 8.16 μM against neuroendocrine cancer cells. The structure activity relationships of all nine compounds were discussed.

Design and Antiproliferative Evaluation of Novel Sulfanilamide Derivatives as Potential Tubulin Polymerization Inhibitors

“…The well-known tubulin polymerization inhibitor CA-4P was used as a control. In [ 24 ], 5-fluorouracil ( 5-Fu ) was selected as the control in the antiproliferative evaluation assay of 1,2,3-triazole derivatives. Therefore, 5-Fu was also used as the reference drug in this MTT assay.…”

Efficient click reaction towards novel sulfonamide hybrids by molecular hybridization strategy as antiproliferative agents

“…Melting points were determined on a Beijing Keyi XT4A apparatus and are uncorrected. NMR spectra were obtained on a Bruker DPX 400 MHz spectrometer ( 1 H NMR at 400 MHz, 13 C NMR at 100 MHz) in DMSO-d 6 using TMS as internal standard. Chemical shifts are given in ppm and coupling constants are given in Hz.…”

“…10 Molecular hybridization strategy is a new concept in drug design and development based on the combination of pharmacophoric moieties of different bioactive substances to produce a new hybrid compound with improved affinity and efficacy, when compared to the parent drugs. 11 Based on the above interesting findings and our continuous quest to synthesize antitumor agents, [12][13][14][15][16] led us to carry out the molecular hybridization of biologically active sulfonamide and 1, 2, 3-triazole to integrate them in one molecular platform to generate new hybrid architecture with the aim of exploring the impact of such modification on the anticancer agents. As shown in Figure 3, a molecular hybridization strategy based on the structures of a bioactive sulfonamide derivative 1 and a bioactive 1, 2, 3-triazole compound5 yielded a scaffold which has three parts: (i) a 1, 2, 3-triazole as a central core, (ii) a substituted phenylsulfonamide (iii) another phenyl sulfonamide attached throughcarbon 4 ( Figure 3).…”

Discovery of 5,6-diaryl-1,2,4-triazines hybrids as potential apoptosis inducers

“…Recently, our group have reported four series of 1,2,3-triazole derivatives as potential antitumor agents (Fig. 2): 1,2,3-triazole-chalcone hybrid 4 inhibited the proliferation of SK-N-SH cancer cells by inducing apoptosis and arresting the cell cycle at the G1 phase [15]; the novel 1,2,3-triazole-chalcone 5 bearing a 4,5-dihydrothiazole showed the potent activity with an IC 50 value of 8.16 µM against neuroendocrine cancer cells [16]; 1,2,3-triazole-dithiocarbamate based selective lysine specific demethylase 1 inactivator 6 inhibited gastric cancer cell apoptosis, invasion, and migration [17]; the steroidal hybrid 7 arrested cell cycle at G2/M phase, induced apoptosis accompanied with decrease of mitochondrial membrane potential [18]. …”