Novel coumarin derivatives containing 1,2,4-triazole, 4,5-dicyanoimidazole and purine moieties: synthesis and evaluation of their cytostatic activity

We report here on the synthesis and in vitro anti-tumor effects of a series of novel 1,2,4-triazole (compounds 3-6), 4,5-dicyanoimidazole (compound 7), and purine (compounds 8-13) coumarin derivatives and their acyclic nucleoside analogues 14-18. Structures of novel compounds 3-18 were deduced from their ¹H- and ¹³C-NMR and corresponding mass spectra. Results of anti-proliferative assays performed on a panel of selected human tumor cell lines revealed that compound 6 had moderate cytostatic activity against the HeLa cell line (IC₅₀ = 35 μM), whereas compound 10 showed moderate activity against the HeLa (IC₅₀ = 33 μM), HepG2 (IC₅₀ = 25 μM) and SW620 (IC₅₀ = 35 μM) cell lines. These compounds showed no cytotoxic effects on normal (diploid) human fibroblasts.     

Synthesis of thiacyanine dyes containing coumarin moieties at benzothiazole rings

New bischromophoric dyes (thiacarbocyanine and thiadicarbocyanine) containing coumarin moieties at each of the two benzothiazole systems, as well as monomethinecyanine containing coumarin moiety at only one heterocyclic system, manifest significant batho-chromic shift compared to relative coumarin-free dyes.     

Synthesis of 1,2,3-benzotriazin-4-one derivatives containing spirocyclic indoline-2-one moieties and their nematicidal evaluation

To discover new chemotypes of nematicides with proper toxicological profiles, a series of novel 1,2,3- benzotriazin-4-one derivatives were synthesized and further bioevaluated. The bioassay results showed that most of the synthesized compounds were endowed with moderate to good control efficacy against Meloidogyne incognita at 10.0 mg/L in vivo. Among them, compounds 6k and 6p displayed 100% inhibitory activities at this concentration, which implied that they could be used as lead compounds for promising nematicides.     

Fluorous solvent‐soluble imaging materials containing anthracene moieties

Highly fluorinated photoresist polymers that can undergo photodimerization reactions were designed using an anthracene‐based monomer. Through the random radical copolymerizations of 6‐(anthracen‐9‐yl)hexyl methacrylate ( AHMA ) and semiperfluorodecyl methacrylate ( FDMA ) with four different compositions, polymers with M_n = 20,000–27,000 (M_w/M_n = 2.0–2.9) were prepared in benzotrifluoride. The polymers, in particular fluorous solvent‐soluble imaging material‐2 ( FSIM‐2 ), showed sufficient solubility in fluorous solvents, including hydrofluoroethers, but were rendered insoluble by UV exposure (365 nm). This photochemical solubility change was evaluated quantitatively by a quartz crystal microbalance technique, along with tracing the chemical reaction by UV–vis spectroscopy. Finally, FSIM‐2 and fluorous solvents were applied to the photolithographic patterning of organic light‐emitting diode pixels. In the patterning protocol involving the lift‐off of resist films in fluorous solvents, FSIM‐2 was recognized as a promising photoreactive material when compared with a reference polymer P(FDMA‐MAMA) , which necessitates acidolysis reactions for lithographic imaging. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1252–1259     

Synthesis and biological evaluation of 3-substituted-indolin-2-one derivatives containing chloropyrrole moieties

Eighteen novel 3-substituted-indolin-2-ones containing chloropyrroles were synthesized and their biological activities were evaluated. The presence of a chlorine atom on the pyrrole ring was crucial to reduce cardiotoxicity. The presence of a 2-(ethyl-amino)ethylcarbamoyl group as a substituent at the C-4' position of the pyrrole enhanced the antitumor activities notably. IC50 values as low as 0.32, 0.67, 1.19 and 1.22 μM were achieved against non-small cell lung cancer (A549), oral epithelial (KB), melanoma (K111) and large cell lung cancer cell lines (NCI-H460), respectively.     

Synthesis and insecticidal evaluation of novel N‐oxalyl derivatives of diacylhydrazines containing methylcarbamate moieties

A series of new N‐oxalyl derivatives of diacylhydrazines containing methylcarbamate moieties were synthesized by the reaction of N‐oxalyl chloride of N‐methylcarbmates with N‐tert‐butyl‐N,N′‐diacylhydrazines in the presence of sodium hydride. The reaction of oxalyl chloride with N‐tert‐butyl‐N, N′‐diacylhydrazines to yield 1,3,4‐oxadiazole and 4‐tert‐butyl‐2‐substituted‐phenyl‐4H‐1,3,4‐oxadiazine‐5,6‐dione was found, and the reaction was studied in some detail. The title compounds were evaluated for molting hormone mimicking activity. The results of bioassay showed that the title compounds exhibit moderate larvicidal activities, and toxicity assays indicated that these compounds can induce a premature, abnormal, and lethal larval molt. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:472–475, 2005; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20135     

Synthesis and characterization of new thiazolidinones containing coumarin moieties and their antibacterial and antioxidant activities

New coumarin derivatives, namely (2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-phenylthiazolidin-3-yl)acetamide, N-(2-(3-methoxyphenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide, 2-(4-methyl-2-oxo-2H-chromen-7-yloxy)-N-(4-oxo-2-(2,3,4trimethoxyphenyl)thiazolidin-3-yl)acetamide and N-(2-(4-bromophenyl)-4-oxothiazolidin-3-yl)-2-(4-methyl-2-oxo-2H-chromen-7-yloxy)acetamide) were synthesized starting from 4-methyl-7-hydroxycoumarin. The structures of the obtained compounds were confirmed by analytical IR and NMR spectra to elucidate the different positions of protons and carbons and as well as theoretical studies (DFT/B3LYP). The new compounds were screened for antibacterial activity. Most of them are more active against E. coli S. aureus and B. subtilis than standard references.     

Synthesis of new 2-pyridinone and thiazole derivatives containing coumarin moiety

Coumarin has shown considerable therapeutic potency because of its versatile biological prosperities. Also, pyridines have been adopted in medicinal chemistry as potent ring. Moreover, several investigations reported the potency of thiazole-containing compounds. So, during this research, new functionalized 2-pyridinone and thiazole derivatives bearing coumarin moiety were aimed to synthesize. Many trials to obtain the 6-amino-2-oxo-pyridine-3,5-dicarbonitriles through the condensation of cyanoacetohydrazone of 3-acetyl coumarin with 2-(arylidene)malononitriles were carried out using different reaction conditions. In all cases, the reaction gave none of the corresponding 2-pyridinone derivatives except the reaction with 2-(benzylidene)-malononitrile afforded product in few yield. Moreover, the reaction of another cyanoacetanilide with the 2-(arylidene)-malononitrile afforded the unexpected arylidene derivatives rather than the expected pyridin-2-one derivatives. Finally, new thiazoles bearing coumarin moiety were synthesized using 3-acetylcoumarin N-(2,4-dimethoxyphenyl)-thiosemicarbazone. Cyclization of thiosemicarbazone derivative with ethyl 2-chloroacetate, chloroacetone or phenacyl bromide afforded in high yields the corresponding derivatives of thiazolidin-4-one, 4-methylthiazole or 4-phenylthiazole, respectively.     

Cytotoxicity, antioxidant, and antimicrobial activities of novel 2-quinolone derivatives derived from coumarin

Coumarins are important and useful compounds with diverse pharmacological properties. New coumarin derivatives namely N-aminoquinoline-2-one 1, 1-((4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)methyleneamino)quinolin-2(1H)-one 2 and 1,1′-(1E,1′E)-(1,4-phenylenebis(methan-1-yl-1-ylidene))bis(azan-1-yl-1-ylidene)diquinolin-2(1H)-one 3, were synthesized and characterized by UV–Vis, FT-IR, and NMR spectra in addition of elemental analysis. The synthesized compounds (2 and 3) show considerable anticancer activity against HEp-2 cell line. Synthesized compounds (2 and 3) were tested against selected types of microbial organisms and showed significant activities. The free-radical scavenging activity of synthesized compounds (2 and 3) have been determined by their interaction with the stable free-radical 1,1-diphenyl-2-picrilhydrazyl (DPPH) and all the compounds have shown encouraging antioxidant activities.     

Synthesis of amino derivatives of 1,3,5-triazines containing hetero- and carbocyclic moieties

Reactions of chloro-sim-triazines with secondary amines containing 1,3-dioxolane and hemdichlorocyclopropane moieties were studied. Structures of amino derivatives of 1,3,5-triazines containing cyclic acetal and cyclopropane moieties were examined.     

Synthesis and antifungal activity of novel sulfone derivatives containing 1,3,4-oxadiazole moieties

A series of new sulfone compounds containing 1,3,4-oxadiazole moieties were synthesized. The structures of these compounds were confirmed by spectroscopic data (IR, 1H- and 13C-NMR) and elemental analyses. Antifungal tests indicated that all the title compounds exhibited good antifungal activities against eight kinds of plant pathogenic fungi, and some showed superiority over the commercial fungicide hymexazol. Among them, compounds 5d, 5e, 5f, and 5i showed prominent activity against B. cinerea, with determined EC?? values of 5.21 μg/mL, 8.25 μg/mL, 8.03 μg/mL, and 21.00 μg/mL, respectively. The present work demonstrates that sulfone derivatives such as 5d containing a 1,3,4-oxadiazole moiety can be used as possible lead compounds for the development of potential agrochemicals.     

Synthesis and cytotoxic evaluation of new colchicine derivatives bearing 1, 3, 4-thiadiazole moieties

In search of novel anticancer agents, a series of N-methyl colchiceinamide derivatives (7a-7i) containing 1,3,4-thiadiazole moieties were synthesized, and their structures were confirmed by spectral analysis. Cytotoxicity of these compounds was evaluated by MTT assay in vitro against four human tumor cell lines, i.e. A2780, A549, BEL7402, and MCF-7. The results indicated that most of the derivatives showed significant anticancer activities, particularly, compounds 7h and 7i showed more potent cytotoxic activities of all screened cancer cells than colchicine.     

Microwave synthesis and thermal properties of polyacrylate derivatives containing itaconic anhydride moieties

ABSTRACT: BACKGROUND: Microwave irradiation as an alternative heat source is now a well-known method in synthetic chemistry. Microwave heating has emerged as a powerful technique to promote a variety of chemical reactions, offering reduced pollution, low cost and offer high yields together with simplicity in processing and handling. On the other hand, copolymers containing both hydrophilic and hydrophobic segments are drawing considerable attention because of their possible use in biological systems. Various copolymer compositions can produce a very large number of different arrangements, producing materials of varying chemical and physical properties. Thus, the hydrophilicity of copolymers can be modified by changing the amount of incorporated itaconic anhydride. RESULTS: A series of methyl methacrylate (MMA) and acrylamide (AA) copolymers containing itaconic anhydride (ITA) were synthesized by microwave irradiation employing a multimode reactor (Synthos 3000 Aton Paar, GmbH, 1400 W maximum magnetron) as well as conventional method. The thermal properties of the copolymers were evaluated by different techniques. Structure-thermal property correlation based on changing the itaconic anhydride ratio was demonstrated. Results revealed that the incorporation of itaconic anhydride into the polymeric backbone of all series affect the thermal stability of copolymers. In addition, the use of the microwave method offers high molecular weight copolymers which lead eventually to an increase in thermal stability. CONCLUSIONS: Microwave irradiation method showed advantages for the produced copolymers compared to that prepared by conventional method, where it can offer a copolymer in short time, high yield, more pure compounds and more thermally stable copolymers, rather than conventional method. Also, microwave irradiation method gives higher molecular weight due to prevention of the chain transfer. Moreover, as the itaconic anhydride content increases the thermal stability and Tg increase due to the decrease in the crystallinity.     

Synthesis of quinazoline derivatives containing veratrole and benzo-15-crown-5 moieties

The condensation of (benzo-15-crown-5)-4-thiocarboxamide with anthranilic acid is studied for the first time. Novel representative of crown ethers incorporating the quinazoline moiety is synthesized. Methylation of (benzo-15-crown-5)-4-thiocarboxamide proceeds anomalously giving (benzo-15-crown-5)-4-carbonitrile. (Benzo-15-crown-5)-4-thiocarboxamide is reacted with thioveratramide in order to compare the reaction paths.Mirzo Ulugbek Tashkent State University, Tashkent 700095, Republic of Uzbekistan; Institute of Plant Chemistry, Academy of Sciences of the Republic of Uzbekistan, Tashkent 700170. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 937–940, July, 1999.     

Synthesis and in vitro study of new coumarin derivatives linked to nicotinonitrile moieties as potential acetylcholinesterase inhibitors

The appropriate pyridine-2(1H)-thiones were reacted with an equivalent amount of 5-(chloromethyl)-2-hydroxybenzaldehyde in ethanol in the presence of potassium hydroxide to give the corresponding 2-hydroxybenzaldehyde derivatives in excellent yields. The latter derivatives were taken as key synthons for the preparation of the target hybrids. Therefore, 2-hydroxybenzaldehydes were reacted with benzoylglycine in acetic anhydride in the presence of fused sodium acetate at 100°C for 6 hours to afford a new series of nicotinonitrile-coumarin hybrids. The in vitro acetylcholinesterase inhibitory activities were estimated for the new coumarins. The results were expressed as the inhibition percentage of the tested hybrids at concentration of 25 nM, compared to donepezil as a reference (inhibition percentage of 70.5). Coumarin hybrids linked to 6-(4-nitrophenyl) or 6-(4-chlorophenyl)-4-phenylnicotinonitrile exhibited more effective inhibitory activities than donepezil with inhibition percentages of 94.1 and 72.3, respectively. The new coumarins were tested for their free radical-scavenging capabilities against DPPH. Furthermore, some new coumarins were tested for in vitro cytotoxic activity against each MCF-10A, MCF-7, Caco2, and HEPG2. The new hybrids showed cytotoxicity in micromolar range (IC₅₀ of 3.5-13.9 μM) against all tested cell lines. These results clearly demonstrated that the hybrids being tested are not cytotoxic at the concentration required to inhibit acetylcholinesterase effectively.     

Catalyst-free synthesis of pyrazole-aniline linked coumarin derivatives and their antimicrobial evaluation

Catalyst-free one-pot CN and CC bond formation is described as a simple and ecofriendly method for the synthesis of pyrazole-aniline linked coumarin derivatives. Employing this protocol, a series of derivatives were synthesized in good to excellent yields and tested against different bacterial strains as well as fungal strains. Most of the compounds exhibited potential antimicrobial activity against both Gram-positive and Gram-negative bacterial strains. Among them, the compounds 4b, 4e, 4?h, 4i and 4?k exhibited promising activity on all the tested bacterial strains with values ranging between 1.9 and 7.8?µg/mL. In addition, these compounds were tested against various fungal strains and were found to exhibit potential antifungal activity. Fascinatingly, among the tested derivatives, the compounds 4e, 4?h and 4i were found to be equipotent to miconazole (positive control) against some of the tested fungal strains. Moreover, these compounds showed promising bactericidal, Candida-cidal and biofilm inhibition activities. Further, mechanistic study was carried out with the most active derivative 4i indicated that these compounds inhibit the ergosterol biosynthesis pathway.     

Synthesis and in-vitro antioxidant activities of some coumarin derivatives containing 1,2,3-triazole ring

A new green protocol was developed for the S-alkylation of 2-mercapto-1,3,4-oxadiazole by the reaction of 5-substituted-2-mercapto-1,3,4-oxadiazole with propargyl bromide in sodium bicarbonate in water. The newly synthesized 5-[(substitutedphenoxy)methyl]-2-[(prop-2-yn-1-yl)sulfanyl]-1,3,4-oxadiazole when reacted with azidomethyl coumarins underwent regioselective reaction yielding 4-(((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethyl)-1H-1,2,3-triazol-1-yl)methyl)-6-methyl)-2H-chromene-2-one or 1-((4-((5-((substitutedphenoxy)methyl)-1,3,4-oxadiazol-2-yl)sulfanylmethy)-1H-1,2,3-triazol-1-yl-)methyl)-3H-benzo[f]chromene-3-one. Structures of the newly synthesized compounds were confirmed by spectral and analytical data. The compounds were screened for their in-vitro antioxidant property.     

去氢枞酸异丙醇胺衍生物的合成及其细胞毒性评价

为了寻找高效的抗肿瘤活性化合物,设计合成了一系列去氢枞酸异丙醇胺类化合物,利用IR、NMR和MS对其结构进行表征。采用噻唑蓝(MTT)法评价了目标化合物对四种不同肿瘤细胞T24(人膀胱移行癌细胞)、HepG2(人肝癌细胞)、SK-OV-3(人卵巢癌细胞)、A549(人肺癌细胞)和LO2(人正常肝细胞)的抗增殖活性。结果表明,部分化合物对肿瘤细胞的抑制作用优于阳性对照顺铂。其中,化合物3d对四种细胞株表现出最好的抗增殖效果,IC₅₀值分为8.10±0.28,8.65±0.10,13.21±0.35和8.24±0.42 μmol.L_-1^{。初步机理研究表明},化合物3d使A549细胞周期阻滞在G1/G0期,并诱导A549细胞凋亡,且呈浓度依赖性。     

Synthesis, antiviral and antifungal bioactivity of 2-cyano-acrylate derivatives containing phosphonyl moieties

Alkyl 2-cyano-3-methylthio-3-phosphonylacrylates were synthesized by the reaction of alkyl 2-cyano-3,3-dimethylthioacrylates with dialkyl phosphites. The structures of the new compounds were characterized by elemental analyses, IR, 1H-, 13C- and 31P-NMR spectral data. These compounds were tested in vitro against pathogenic fungi, namely, Fusarium graminearum, Cytospora mandshurica and Fusarium oxysporum. Amongst all compounds, 2d and 2t were found to be effective against the tested fungi at 50 microg/mL. A half-leaf method was used to determine the in vivo protective, inactivation and curative efficacies of the title products against tobacco mosaic virus (TMV). Title compounds 2a and 2b were found to possess good in vivo curative, protection and inactivation effects against TMV with inhibitory rates at 500 mg/L of 60.0, 89.4 and 56.5 and 64.2, 84.2 and 61.2 %, respectively. To the best of our knowledge, this is the first report on the antiviral and antifungal activity of alkyl 2-cyano-3-methylthio-3-phosphonylacrylates.