Despite the discovery of many chemotherapeutic drugs that prevent uncontrolled cell division processes in the last century, many studies are still being carried out to develop drugs with higher anticancer efficacy and lower level of side effects. Herein, we designed, synthesized, and characterized six novel coumarin-triazole hybrids, and evaluated for anticancer activity of the one with the highest potential against the breast cancer cell line, MCF-7 and human cervical cancer cell line, human cervical adenocarcinoma (HeLa). Compound 21 which was the coumarin derivative including phenyl substituent with the lowest IC50 value displayed the highest cytotoxicity against the studied cancer cell line. Furthermore, the potential use of poly (lactic-co-glycolic acid) nanoparticles (PLGA NPs) prepared by the emulsifying solvent evaporation method as a platform for a drug delivery system was studied on a selected coumarin derivative 21. This coumarin derivative-loaded PLGA NPs were produced with an average size of 225.90 +/- 2.96 nm, -16.90 +/- 0.85 mV zeta potential, and 4.12 +/- 0.90% drug loading capacity. The obtained 21-loaded PLGA nanoparticles were analyzed spectroscopically and microscopically with FT-IR, UV-vis, and scanning electron microscopy as well as thermogravimetric analysis, Raman, and x-ray diffraction. The in vitro release of 21 from the nanoparticles exhibited a controlled release profile just over one month following a burst release in the initial six hours and in addition to this a total release ratio of %50 and %85 were obtained at pH 7.4 and 5.5, respectively. 21-loaded PLGA nanoparticles displayed remarkably effective anticancer activity than 21. The IC50 values were determined as IC50 (21-loaded PLGA nanoparticles): 0.42 +/- 0.01 mg ml-1 and IC50 (free 21 molecule): 5.74 +/- 3.82 mg ml-1 against MCF-7 cells, and as IC50 (21-loaded PLGA nanoparticles): 0.77 +/- 0.12 mg ml-1 and IC50 (free 21 molecule): 1.32 +/- 0.31 mg ml-1 against HeLa cells after the incubation period of 24 h. Our findings indicated that triazole-substituted coumarins may be used as an anticancer agent by integrating them into a polymeric drug delivery system providing improved drug loading and effective controlled drug release.

Abstract Several high solid content waterborne polyurethane dispersions (WPUDs) with the combination of anionic and nonionic stabilization were synthesized by polyaddition reaction using isophorone diisocyanate (IPDI), trimethylol propane (TMP) and 1,6-hexanediol (HDO) as the hard segments, polypropylene glycol with molecular weight of 2000 Da (PPG-2000), and polytetramethylene ether glycol with molecular weight of 2000 Da (PTMG-2000) as the soft segments, anionic diol dimethylol propionic acid (DMPA) and nonionic diol Y-mer N 120 (NID) as the donors of hydrophilic groups. The chain extension reaction between residual NCO groups was made by using hydrazine (HYD). The effects of the combination of anionic and nonionic monomer and macrodiol types on the performance of the WPUDs were studied in terms of particle size distribution and dispersion stability. The results showed that the WPUDs exhibited narrow particle size distribution, good appearance and good mechanical properties. Graphical Abstract

A new coumarin derivative, 7-((8-(4-benzylpiperidin-1-yl)octyl)oxy)-4-methyl-2H-chromen-2-one (C3), was synthesized by two-step alkylation reaction of 7-hydroxy-4-methyl coumarin. The structure and purity of the compound were characterized by its 1H and 13C NMR, FT-IR and LC-MS spectral data. The DNA binding interaction of C3 was evaluated using UV–vis spectrophotometric and viscosimetric methods. These experiments showed that C3 was bound in intercalative mode. The antioxidant activity of C3 was evaluated by the DPPH method, the antioxidant activity results displayed that C3 had DPPH radical scavenging effect. The possible mechanism of antioxidant and anticancer activity of C3 was investigated via molecular docking by using two enzymes CYP450 and EGFR as receptors. The C3 also tended a good antioxidant ability based on the result of the molecular docking analysis, with good binding affinity values (-7.82 kcal/mol) and binding site interactions. Molecular Dynamics (MD) simulation was implemented to elucidate the interactions with the protein–ligand complex in 20 ns. The ADMET analyzes which paved the way for us to predict C3 as a drug candidate were also performed. All experimental and theoretical results showed that the compound C3 was a potential drug candidate as an antioxidant and anticancer agent.

Seven novel proline and 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA) based diamides were synthesized successfully by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were performed by the reactions of aliphatic ketones and various aromatic aldehydes. Especially, (S)-N-((S)-1-(morpholinoamino)-1-oxo-3-phenylpropan-2-yl)pyrrolidine-2-carboxamide (9e) showed good catalytic activities in water at room temperature in the presence of benzoic acid cocatalyst. The enantioselectivities were upto 89.6%, the diastereomeric ratios were upto 92/8, and yields were upto 97.3%. This catalyst showed its best catalytic activities in water; this is also an important contribution to green chemistry requirements.

The aldol reaction which is the most important one among the C-C bond forming reactions, is widely used by synthetic organic chemists to obtain β-hydroxycarbonyl compounds which are important starting components for biologically active compounds in optically pure form. In this research, five Pro-Phe derivatives were synthesized by simple amidation reactions and characterized by their spectral data. Their catalytic activities in asymmetric aldol reaction were investigated. The catalytic activity studies were performed with aliphatic ketones and various aromatic aldehydes. Especially, (S)- methyl 3-mercapto-2-((S)-3-phenyl-2-((S)-pyrrolidine-2-carboxamido)propanamido)propanoate showed good catalytic activities in water at 0oC in the presence of p-nitrobenzoic acid cocatalyst. The enantioselectivities were up to 90.4%, the diastereomeric ratios were up to 97/3 and yields were 99%. The results showed that these organocatalysts were promising organocatalysts for aldol reaction. Besides, this catalyst showed its best catalytic activities in water which is also an important contribution to green chemistry requirements.

In this study, the aim was computer-aided design of a new anti-cancer drug molecule. For this purpose, 7-hydroxy-8-(((1-hydroxy-3-phenylpropan-2-yl)imino)methyl)-4-(trifluoromethyl)-2H-chromen-2-one (D3) was synthesized by the condensation reaction. Its characterization studies were performed by NMR, FTIR, MS and UV spectral data. Anti-cancer activity of D3 was examined on MCF-7, HeLa and Mat-Lylu cell lines, and it was found that D3 showed cytotoxic activity in all cell lines. Mutagenity of D3 was determined by Ames/Salmonella assay, and it was found that it had no mutagenic effect on S. ty-phimurium TA98 and TA100 strains. Antioxidant activity of D3 was also revealed. Besides, the interaction of D3 with DNA was investigated by the UV titration method. Experimental results showed D3 binds to DNA by intercalation or groove linking. Moreover, molecular docking approach was used to elucidate the atomic level interaction between the synthesized compound and DNA; thus, the atomic level behavior of the compound in the binding site of DNA was characterized and its binding properties were determined. In addition, the physicochemical and pharmacokinetic properties of the synthesized compound were per -formed using ADMET and frontier orbital analyses. In conclusion, according to both in vitro and in silico findings, it can be suggested that D3 may be used as a new anti-cancer drug for breast, cervical and prostate cancers. (c) 2021 Elsevier B.V. All rights reserved.

Herein, a novel coumarin-based fluorescent probe (FS3) was designed, synthesized, and characterized. It exhibited significant fluorescence quenching in the presence of Zn2+ ions. Just a minor alteration occurred in the fluorescence intensity of FS3 in the presence of other metals studied. The limit of detection for the determination of Zn2+ by FS3 was calculated to be 3.43 x 10(-9) M. Since the Job's graph of 1/(F-0-F) and 1/[Zn2+] had a linear fit, it was determined that the binding stoichiometry between the FS3 and Zn2+ was 1:1. The association constant of the system was found to be 2.39 x 10(4) M-1 and confirmed by ESI-MS and FT-IR. It was demonstrated that the developed highly reversible sensor system works by performing real sample analysis. Moreover, the FS3 which has shown no toxicity and displayed a strong fluorescence image will act as an efficient and non-destructive sensor for the determination of Zn2+ in living organisms. (C) 2021 Elsevier Ltd. All rights reserved.

New di- or triamide organocatalysts derived from (L)-proline were synthesized and successfully used in the direct asymmetric aldol reaction of aliphatic ketones and aromatic aldehydes in water at 0oC in the presence of benzoic acid as co-catalyst. (S)-methyl-2-((S)-3-hydroxy-2-((S)-3-pyrrolidine-2-carboxamido)propanamido)-3-phenylpropanoate (7c) as organocatalyst showed best results under these reaction conditions, and good diastereoselectivities (up to 99%), enantioselectivities (up to 98%) and yields (up to 91%) were observed.

The aim of this study was to develop a novel nanosize drug candidate for cancer therapy. For this purpose, (S)-methyl 2-[(7-hydroxy-2-oxo-4-phenyl-2H-chromen-8-yl)methyleneamino]-3-(1H-indol-3-yl)propanoate (ND3) was synthesized by the condensation reaction of 8-formyl-7-hydroxy-4-phenylcoumarin with l-tryptophan methyl ester. Its controlled release formulation was prepared and characterized by different spectroscopic and imaging methods. The cytotoxic effects of ND3 and its controlled release formulation were evaluated against MCF-7 and A549 cancer cell lines, and it was found that both of them have a toxic effect on cancer cells. For drug design and process development, the molecular docking analysis technique helps to clarify the effects of some DNA-targeted anticancer drugs to determine the interaction mechanisms of these drugs on DNA in a shorter time and at a lower cost. By using the molecular docking analysis and DNA binding assays, the interaction between the synthesized compound and DNA was elucidated and non-binding interactions were also determined. To predict the pharmacokinetics, and thereby accelerate drug discovery, the absorption, distribution, metabolism, excretion and toxicity values of the synthesized compound were determined by in silico methods.

Sulfuric acid immobilized on silica gel is used as an efficient catalyst in the synthesis of N-substituted pyrrole derivatives by the Clauson–Kaas pyrrole synthesis. The solvent free reaction mixture is stirred by grinding. Within very short reaction time the process leads to the corresponding products without any decomposition recorded.

Background: Proline and its derivatives are versatile organocatalysts for many reactions. Especially prolinamide derivatives have been prepared and investigated in aldol reaction successfully. Generally, derivatizations have been made on side chain of proline to develop new effective catalysts. But, there are only few examples of different cyclic systems other than pyrrolidine ring used as chiral organocatalysts. Method: The methodology for this study was the synthesis of new thiazolidine-4-carboxylic acid based organocatalysts and investigation of their catalytic activities in asymmetric direct aldol reactions. Results: New thiazolidine based organocatalysts 6a-g [substituted (4R)-N-[(2S)-1-amino-1-oxo-3-phenyl- 2-propyl]-4-thiazolidinecarboxamides] were synthesized and characterized. Their catalytic activity studies in asymmetric direct aldol reactions of aliphatic ketones with arylaldehydes were performed. Among the catalysts investigated in this study, especially methyl (2S)-3-phenyl-2-[(2S)-3-phenyl- 2-[(4R)-thiazolidine-4-carboxamido]propanamido]propanoate (6a) and (4R)-N-[(2S)-1-(benzhydrylamino)-1-oxo-3-phenyl-2-propyl]-4-thiazolidinecarboxamide (6b) gave the best diastereoselectivities (up to 91%), enantioselectivities (up to 88%) and yields (up to 94%) when different aliphatic ketones and aromatic aldehydes with electron withdrawing groups were used. Conclusion: Some new organocatalysts derived from thiazolidine-4-carboxylic acid were designed, synthesized, and successfully used in the direct asymmetric aldol reaction of aliphatic ketones and aromatic aldehydes under solvent free conditions. The results showed that these new products were promising organocatalysts for aldol reaction.

New proline diamide organocatalysts with Pro-Phe peptide bonds were synthesized and their catalytic activities in asymmetric direct aldol reactions of aliphatic ketones with aromatic aldehydes were investigated. Catalyst 6a showed good enantioselectivity at 0°C in the presence of p-nitrobenzoic acid as cocatalyst in water.

Catalytic activities of (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (THIQA)-based mono- and dipeptides and their L-proline analogs in asymmetric aldol reaction were investigated. THIQA-based dipeptides showed better enantioselectivity than proline analogs, whereas proline-based dipeptides gave higher yield in the aldol reaction of cyclohexanone with several aldehydes in dichloromethane at -10 degrees C in the presence of benzoic acid. (C) 2014 Elsevier Ltd. All rights reserved.

The catalytic potential of chiral proline amides and pyridinium salts in the aldol condensation in water was investigated. The aldol reactions of acetone with various aromatic aldehydes were carried out in water by using proline amide derivatives and pyridinium salts derived from chiral pyridine derivatives for the first time. The products were obtained in good yields within short reaction times.

ChemInformVolume 45, Issue 36 Preparative Organic Chemistry ChemInform Abstract: Evaluation of Mono- and Dipeptides as Organocatalysts for Enantioselective Aldol Reaction. Cigdem Yolacan, Cigdem Yolacan Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this authorMurat Emrah Mavis, Murat Emrah Mavis Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this authorFeray Aydogan, Feray Aydogan Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this author Cigdem Yolacan, Cigdem Yolacan Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this authorMurat Emrah Mavis, Murat Emrah Mavis Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this authorFeray Aydogan, Feray Aydogan Dep. Chem., Yildiz Tech. Univ., TR-34010 Esenler, Istanbul, Turk.Search for more papers by this author First published: 21 August 2014 https://doi.org/10.1002/chin.201436021Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume45, Issue36September 9, 2014 RelatedInformation

A new procedure to synthesize the N-substituted pyrrole derivatives by Clauson Kaas reaction catalyzed by acidic ionic liquid under microwave irradiation was developed. This procedure provides several advantages such as high yield, clean product formation, and short reaction time.

Long chain dicationic ammonium salts (1a-1c), easily prepared from tert-amines and dihaloalkanes, were successfully used as efficient phase-transfer catalysts in the Michael addition reaction of various active methylene compounds to 2-cyclohexenone without solvent under ultrasonic irradiation. The investigated dicationic salts were more effective than monocationic tetrabutylammonium bromide, with short reaction times and high yields. This methodology was established under phase-transfer catalytic conditions and ultrasonic effects with many advantages, including the easy and cost-effective synthesis of the catalyst, mild reaction conditions, short reaction times, good yields, simple work-up procedures. and environmental friendliness.

The synthesis of alpha-aminonitriles was successfully accomplished by the 1-pot 3-component reaction of several aldehydes with (S) alpha-phenylethylamine and sodium cyanide in water in the presence of montmorillonite K10 and dicationic phosphonium salt under ultrasonic effect with good yields and moderate diastereoselectivities.

The catalytic potential of imidazolium salts in the benzoin condensation was investigated. Various aromatic aldehydes were tested in the benzoin condensation under the optimised protocol to afford α-hydroxyketones using N-heterocyclic carbenes derived from mono- and dicationic imidazolium salts. The products were obtained in good yields within short reaction times. Dicationic imidazolium salts with a long aliphatic chain between the imidazole rings were found to be more effective pre-catalysts for the benzoin condensation in comparison to the corresponding monocationic salts having the same aliphatic chain length.