“…[20][21][22] The successful completion of these reactions was found to substantially depend on the catalyst that was used. For example, the interaction of hydrazides 1a-с with 2,4-pentanedione under the conditions described in earlier publications [14][15][16][17][18][19] (catalyst hydrochloric acid, solvent i-PrOH) was accompanied by rapid hydrolysis of compounds 1а-с, followed by esterification of the intermediate pyrrolidone carboxylic acids and resulting in the isolation of the respective isopropyl esters 4a-c (Scheme 2).…”
Section: Methodsmentioning
confidence: 97%
“…The synthesis of such substituted 2-pyrrolidones has been described only in a very limited number of literature sources: 1-hetaryl-4-(pyrazol-1-ylcarbonyl)-2-pyrrolidones were obtained in good yields by cyclocondensation of 1-hetaryl-2-oxopyrrolidine-4-carbohydrazides with 2,4-pentanedione ( acac ) in i -PrOH medium in the presence of a catalytic amount of hydrochloric acid 14 – 19 (Scheme 1 ). Scheme 1 …”
mentioning
confidence: 99%
“…The synthesis of such substituted 2-pyrrolidones has been described only in a very limited number of literature sources: 1-hetaryl-4-(pyrazol-1-ylcarbonyl)-2-pyrrolidones were obtained in good yields by cyclocondensation of Chemistry of Heterocyclic Compounds 2022, 58 (11), 598-607 Synthesis, structure, and biological activity of 4-hetaryl-2-pyrrolidones containing a pyrazole ring 1-hetaryl-2-oxopyrrolidine-4-carbohydrazides with 2,4-pentanedione (acac) in i-PrOH medium in the presence of a catalytic amount of hydrochloric acid [14][15][16][17][18][19] (Scheme 1).…”
Single diastereomers of 4-hetaryl-2-pyrrolidone-3(5)-carbo- and 2-[4-hetaryl-2-pyrrolidon-1-yl]acetohydrazides were used in reactions with 2,4-pentanedione, providing (3
R*
,4
S*
)-3-, (4
R*
,5
R*
)-5-(3,5-dimethyl-1
H
-pyrazole-1-carbonyl)- and 1-[2-(3,5-dimethyl-1
H
-pyrazol-1-yl)-2-oxoethyl]-4-hetaryl-2-pyrrolidones. The structures of the synthesized compounds were confirmed by spectral methods and X-ray structural analysis. Some of the obtained compounds were shown to possess nootropic and anxiolytic activity.
Supplementary Information
The online version contains supplementary material available at 10.1007/s10593-022-03140-4.
“…[20][21][22] The successful completion of these reactions was found to substantially depend on the catalyst that was used. For example, the interaction of hydrazides 1a-с with 2,4-pentanedione under the conditions described in earlier publications [14][15][16][17][18][19] (catalyst hydrochloric acid, solvent i-PrOH) was accompanied by rapid hydrolysis of compounds 1а-с, followed by esterification of the intermediate pyrrolidone carboxylic acids and resulting in the isolation of the respective isopropyl esters 4a-c (Scheme 2).…”
Section: Methodsmentioning
confidence: 97%
“…The synthesis of such substituted 2-pyrrolidones has been described only in a very limited number of literature sources: 1-hetaryl-4-(pyrazol-1-ylcarbonyl)-2-pyrrolidones were obtained in good yields by cyclocondensation of 1-hetaryl-2-oxopyrrolidine-4-carbohydrazides with 2,4-pentanedione ( acac ) in i -PrOH medium in the presence of a catalytic amount of hydrochloric acid 14 – 19 (Scheme 1 ). Scheme 1 …”
mentioning
confidence: 99%
“…The synthesis of such substituted 2-pyrrolidones has been described only in a very limited number of literature sources: 1-hetaryl-4-(pyrazol-1-ylcarbonyl)-2-pyrrolidones were obtained in good yields by cyclocondensation of Chemistry of Heterocyclic Compounds 2022, 58 (11), 598-607 Synthesis, structure, and biological activity of 4-hetaryl-2-pyrrolidones containing a pyrazole ring 1-hetaryl-2-oxopyrrolidine-4-carbohydrazides with 2,4-pentanedione (acac) in i-PrOH medium in the presence of a catalytic amount of hydrochloric acid [14][15][16][17][18][19] (Scheme 1).…”
Single diastereomers of 4-hetaryl-2-pyrrolidone-3(5)-carbo- and 2-[4-hetaryl-2-pyrrolidon-1-yl]acetohydrazides were used in reactions with 2,4-pentanedione, providing (3
R*
,4
S*
)-3-, (4
R*
,5
R*
)-5-(3,5-dimethyl-1
H
-pyrazole-1-carbonyl)- and 1-[2-(3,5-dimethyl-1
H
-pyrazol-1-yl)-2-oxoethyl]-4-hetaryl-2-pyrrolidones. The structures of the synthesized compounds were confirmed by spectral methods and X-ray structural analysis. Some of the obtained compounds were shown to possess nootropic and anxiolytic activity.
Supplementary Information
The online version contains supplementary material available at 10.1007/s10593-022-03140-4.
“…The reaction of the latter with the appropriate β-ketoester ester using sulfuric acid produced the coumarins 3a-c. Basic hydrolysis of the carbamates 3a-c delivered the desired 7-amino-4-substituted coumarins 4a-c in good yields 22 .…”
The incidence of obesity-related diseases like diabetes, cardiovascular diseases, and different types of cancers shed light on the importance of dietary control as preventive and treatment measures. However, long-term dietary control is challenging to achieve in most individuals. The use of energy restriction mimetic agents (ERMAs) as an alternative approach to affect the energy machinery of cancer cells has emerged as a promising approach for cancer therapy. ERMAs limit the high need for energy in rapidly growing tumor cells, with their survival rate strongly dependent on the robust availability of energy. In this context, initial phenotypic screening of an in-house pilot compound library identified a new class of aminothiazole anchored on coumarin scaffold as potent anticancer lead drug candidates with potential activity as ERMA. The identified chemotypes were able to inhibit glucose uptake and increase ROS content in cancer cells. Compounds 9b, 9c, 9i, 11b, and 11c were highly active against colorectal cancer cell lines, HCT116 and HT-29, with half-maximal inhibitory concertation (IC 50 ) range from 0.25 to 0.38 µM. Further biological evaluations of 9b and 9f using Western blotting, caspase activity, glucose uptake, ROS production, and NADPH/NADP levels revealed the ability of these lead drug candidates to induce cancer cell death via, at least in part, energy restriction. Moreover, the assessment of 9b and 9f synergistic activity with cisplatin showed promising outcomes. The current work highlights the significant potential of the lead compounds, 9b, and 9f as potential anticancer agents via targeting the cellular energy machinery in cancer cells.www.nature.com/scientificreports www.nature.com/scientificreports/ on this in brief: If our scaffolds possess a similar mechanism of action as that of OSU-CG12 (Fig. 1), then an electron-withdrawing group on the phenyl ring of our motifs should mimic that of the phenyl ring in OSU-CG12. Therefore, compounds with electron-withdrawing groups (9a, 9b, 9c, and 9f) are the most active as anticancer agents. Furthermore, the cyclohexyl group in OSU-CG12 is not substituted. Therefore, bulkier groups on its analogue, the coumarin ring in our motifs, should not be tolerated and, therefore, less potent as anticancer.
Biological evaluationCell viability of human colorectal cancer cell lines. The potential cytotoxicity of 24 candidate compounds was initially evaluated at a single concentration level (5 μM). Then a full dose-response curve was plotted for each compound against different colorectal cancer cell lines (HCT116 and HT-29) by MTT assay after 72 h treatments. The half-maximal inhibitory concertation (IC 50 ) values after 72 h treatment are summarized in Table 1. 4-hydroxycoumarin, OSU-CG5, and OSU-CG12 were used as positive controls. Most compounds exhibited higher potency in comparison to the positive controls except 9h (>30 µM),10a (>30 µM) and 10e (13.06 ± 1.39), in HT-29 and 9h (>30 µM), 10a (>30 µM), 10e (>30 µM) 10f (10.3 ± 3.15), 10i (13.49 ± 0.20), 11a (6.76 ± 0....
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