Design, Synthesis and Anti-Depressant Activity of Some Novel Coumarin Derivatives
Twenty-seven 3, 7-disubstituted coumarin derivatives were designed, synthesized, and evaluated in vitro as anticancer agents. Structure-Activity Relationship. A series of novel coumarin derivatives carrying 1,2,4-triazole or 1,2 The derivatives 4c and 8c exhibited marked anticancer activity with IC50 values The structures of the newly synthesized compounds were Finally, there was a good correlation between the docking studies and the biological profiles. Chen, J.; Yu, Y.; Li, S.; Ding, W. Resvertrol and coumarin: Novel agricultural M.K. Synthesis and pharmacological evaluations of 4-hydroxycoumarin derivatives as a new class D. Design, synthesis and biological evaluation of some new coumarin Synthesis, structure–activity relationships (SAR) and in Silico studies of.
The melting point was determined by using Kjeldahl flask containing liquid paraffin. Procedure for scheme Synthesis of 3-Acetyl-2H-Chromenone: A mixture of salicyaldehyde 0. To this mixture 0. The mixture was maintained at freezing temperature for minutes resulting in a yellow colored solid mass, which was separated out. It was recrystallized from ethanol to get the target compound I. Synthesis of 3- Bromoacetyl -2H-Chromenone: To a solution of compound I 0.
The mixture was warmed to decompose an addition product. The mixture was heated for 20min, cooled and filtered to get a solid mass which on washing with ether gave the desired product.
It was recrystallized from acetic acid to give colorless needles II. A suspension of compound II 0.
It was filtered, washed with ethanol and then boiled with water containing sodium acetate which yielded the target compound. The product obtained was recrystallized with ethanol III Figure 1.
Pharmacology Rat-Sprague Dawley having weight gm and are weeks old, was obtained from National Institute of Bioscience, Pune. They were allowed to acclimatize for four days before the experiments and were given free access to Standard sterilized extruded rodent diet was provided ad libitum, Reverse Osmosis water treated with UV light was provided ad libitum in autoclaved polypropylene bottles and Autoclaved corn cob was used as bedding material.
Standard operating procedures of the Prado Pvt. Antidepressant activity forced swim test in rat Porsolt et al.
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Taking into consideration the previously reported tyrosine kinases CDK2 inhibitory activity of the structurally related chromene anticancer agents genistein [ 34 ] and quercetin [ 35 ], we docked the synthesized compounds in CDK2 active site. To validate and specify the target protein for the antitumor activity of newly synthesized triazolyl coumarin derivatives, CDK2 protein was selected and downloaded from the protein data bank PDB ID: Similarly, docking conformation of the active compound 8c showed good interactions with the active site residues of this protein.
Finally, there was a good correlation between the docking studies and the biological profiles.
The excess phosphoryl chloride was distilled off under reduced pressure. The resulted residue was triturated with dry pyridine 2 mLand ice-cold water mL was added and the mixture was kept for 10 minutes. The precipitated crude product was filtered, washed with water, and crystallized from ethanol to yield 2.
Design, synthesis and structure-activity relationship of novel coumarin derivatives.
On cooling, the precipitated crude products were filtered, dried, and recrystallized from DMF-EtOH to afford compounds 4a—c as yellowish brown powders. Method A To a suspension of the arylideneamino analogues 4a—c 50 mmolin dry acetonitrile 70 mLiodine 1.
Upon completion of the reaction, the reaction mixture was poured onto ice-cold water mLand a solution of sodium thiosulfate was added to destroy excess iodine. Method B A mixture of the appropriate carboxylic acid 50 mmol3-[ coumarinyl methyl]amino-1H-1,2,4-triazole-5 4H -thione 3 1. On cooling, crushed ice g was cautiously added, and the mixture was stirred for 30 minutes.
The separated crude product was filtered, washed with water then with saturated sodium hydrogen carbonate solution and finally with water, dried, and crystallized from DMF-EtOH.
On cooling, the reaction mixture was poured onto ice-cold water mLand the mixture was slightly acidified with hydrochloric acid. The precipitated crude product was filtered, washed with water, dried, and crystallized from dioxin to yield 2. Water 15 mL was added, and the mixture was stirred for further 30 minutes. The precipitated crude product was filtered, washed with water, dried, and crystallized from ethanol to yield 1.
Synthesis of Novel 1,2,4-Triazolyl Coumarin Derivatives as Potential Anticancer Agents
The excess DMF was then distilled off in vacuo, and the solid residue was triturated with water 20 mL. The separated solid precipitate was filtered, washed with water, and crystallized from DMF-Ethanol to yield compounds 8a—c as reddish brown crystals. Conclusions In the current study, a novel series of triazolyl coumarin derivatives were synthesized and evaluated as anticancer agents against human colorectal cancer cell line HCT The compounds 4c and 8b exhibited marked cytotoxic activity with The molecular docking studies of the active compounds revealed that these compounds might act via inhibition of tyrosine kinases CDK2.
- Journal of Chemistry
The active compounds are considered to be good candidates as newer anticancer agents, and further studies including preparation of newer analogues and toxicity testing are required for optimization of the activity which are being undertaken.
Data Availability The data used to support the findings of this study are available from the corresponding author upon request. Conflicts of Interest The authors declare that they have no conflicts of interest.
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