Ruo-Han Zhao

Design, synthesis and antiproliferative activity studies of novel dithiocarbamate–chalcone derivates

A series of novel dithiocarbamate-chalcone derivates were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell lines (EC-109, SK-N-SH and MGC-803). Majority of the synthesized compounds exhibited moderate to potent activity against all the cancer cell lines assayed. Particularly, compounds II2 and II5 exhibited the excellent growth inhibition against SK-N-SH with IC50 values of 2.03μM and 2.46μM, respectively. Further mechanism studies revealed that compound II2 could obviously inhibit the proliferation of SK-N-SH cells by inducing apoptosis and arresting the cell cycle at G0/G1 phase.

Design, synthesis and antiproliferative activity studies of 1,2,3-triazole–chalcones

A series of 1,2,3-triazole–chalcone hybrids were designed, synthesized and evaluated for their antiproliferative activity against three selected cancer cell lines (SK-N-SH, HepG-2 and MGC-803). Most of the synthesized compounds exhibited moderate to good activity against all the cancer cell lines selected. Particularly, compound 12k showed the most excellent antiproliferative activity with an IC50 value of 1.53 μM against SK-N-SH cancer cells. The mechanism studies revealed that compound 12k inhibited the proliferation of SK-N-SH cancer cells by inducing apoptosis and arresting the cell cycle at the G1 phase.

Synthesis of novel antiproliferative 1,2,3-triazole hybrids using the molecular hybridisation approach

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, synthesis and antiproliferative evaluation of 3-aminopropyloxy derivatives of chalcone

A series of 3-aminopropyloxy derivatives of chalcone were synthesised and evaluated for their antiproliferative activity against liver, gastric and neuroendocrine cancer cell lines. Most of the synthesised compounds exhibited moderate to good activity against all three cancer cell lines, but in particular, a 3-(pyrrolidin-1-yl)propyloxy chalcone containing a 3,4,5-trimethoxyphenyl group showed the highest antiproliferative activity with an IC50 value of 2.74 μM against liver cancer cells.

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

A series of sulfanilamide-1,2,3-triazole hybrids were designed by a molecular hybridization strategy and evaluated for antiproliferative activity against three selected cancer cell lines (MGC-803, MCF-7 and PC-3). The detailed structure-activity relationships for these sulfanilamide-1,2,3-triazole hybrids were investigated. All these sulfanilamide-1,2,3-triazole hybrids exhibited moderate to potent activity against all cell lines. In particular 4-methyl-N-((1-(3-phenoxybenzyl)-1H-1,2,3-triazol-4-yl)methyl)benzenesulfonamide (11f) showed the most potent inhibitory effect against PC-3 cells, with an IC50 value of 4.08 μM. Furthermore, the tubulin polymerization inhibitory activity in vitro of compound 11f was 2.41 μM. These sulfanilamide hybrids might serve as bioactive fragments for developing more potent antiproliferative agents.

Design and antiproliferative activity of N-heterocycle-chalcone derivatives

Nine chalcone derivatives containing an N-heterocyclic compound attached by its nitrogen atom to one of the benzene rings were prepared and evaluated for their antiproliferative activity against liver, gastric and neuroendocrine cancer cell lines. Most of the synthesised compounds exhibited moderate to good activity against all three cancer cell lines, but in particular, a chalcone containing a 4-(imidazol-1-yl)phenyl group and a 3,4,5-trimethoxyphenyl group showed the highest antiproliferative activity with an IC50 value of 5.39 μM against liver cancer cells.

Structure-Activity Relationship Studies of β -Lactam-azide Analogues as Orally Active Antitumor Agents Targeting the Tubulin Colchicine Site

We have synthesized a series of new β-lactam-azide derivatives as orally active anti-tumor agents by targeting tubulin colchicine binding site and examined their structure activity relationship (SAR). Among them, compound 28 exhibited the most potent antiproliferative activity against MGC-803 cells with an IC50 value of 0.106 μM by induction of G2/M arrest and apoptosis and inhibition of the epithelial to mesenchymal transition. 28 acted as a novel inhibitor of tubulin polymerization by its binding to the colchicine site. SAR analysis revealed that a hydrogen atom at the C-3 position of the β-lactam was required for the potent antiproliferative activity of β-lactam-azide derivatives. Oral administration of compound 28 also effectively inhibited MGC-803 xenograft tumor growth in vivo in nude mice without causing significant loss of body weight. These results suggested that compound 28 is a promising orally active anticancer agent with potential for development of further clinical applications.

Molecular diversity of phenothiazines: design and synthesis of phenothiazine–dithiocarbamate hybrids as potential cell cycle blockers

Novel phenothiazine–dithiocarbamate analogues were designed by molecular hybridization strategy and synthesized and evaluated for their anticancer activity in vitro against three selected cancer cell lines (EC-109, MGC-803, and PC-3). The preliminary structure–activity relationship (SAR) for this phenothiazine–dithiocarbamate hybrids is explored. Among all analogues, 2-oxo-2-(10H-phenothiazin-10-yl)ethyl 4-ethylpiperazine-1-carbodithioate (8a) showed the most potent inhibitory activity with an

Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways

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