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Synthesis of novel 2-Thioxothiazolidin-4-one and thiazolidine-2, 4-dione derivatives as potential anticancer agents

A variety of novel thiazolidine derivatives (2-Thioxothiazolidin-4-one and thiazolidine-2, 4-dione derivatives) have been prepared by using 2,4-diphenyl-2Hchromene- 3-carbaldehyde and its derivatives as starting materials. This is the first example of the preparation of thiazolidine derivatives through this novel method. Structure evolution of the resulting thiazolidine derivatives leads to anticancer agents. Our preliminary data for some model compounds on three cancer cell lines (MCF7, A549 and B-16) suggested reasonable anticancer activity against the A549 and B-16 cell lines, with IC50 values of 20.7 and 20.4 muM, respectively. This method is operationally simple and works with a diverse range of substrates.

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Awesome Chemistry Experiments For 1,1-Dioxo-isothiazolidine

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PYRAZOLO[1,5-A]PYRIMIDINES AS ANTIVIRAL AGENTS

The invention provides compounds and pharmaceutically acceptable salts and esters and compositions thereof, for treating viral infections. The compounds and compositions are useful for treating Pneumovirinae virus infection including Human respiratory syncytial virus infections.

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Extended knowledge of 76186-04-4

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Computer-Guided total synthesis of natural products. Recent examples and future perspectives

Quantum chemical calculations of nuclear magnetic resonance (NMR) shifts and coupling constants have been extensively employed in recent years mainly to facilitate structural elucidation of organic molecules. When the results of such calculations are used to determine the most likely structure of a natural product in advance, guiding the subsequent synthetic work, the term ?computer-guided synthesis? could be coined. This review article describes the most relevant examples from recent literature, highlighting the scope and limitations of this merged computational/experimental approach as well.

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Discover the magic of the 2682-49-7

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Synthesis of some 5-(substituted benzylidene)-3-phenyl-2-phenylimino-1,3-thiazolidin-4-ones under ultrasound irradiation

Recently, we have synthesized environmental benign one pot synthesis of 5-(Substituted Benzylidene)-3-Phenyl-2-Phenylimino-1,3-Thiazolidin-4-Ones (a-f) under Ultrasound irradiation by cyclization of 1,3 -diphenylthiourea with a-halo acids in presence of sodium acetate in absolute ethanol for 10-15 minute. The crude compound was purified by silica gel column chromatography using n-hexane and ethyl acetate as solvent system and recrystalised from ethanol. The synthesized compounds have been screened in vitro for their antimicrobial activity against S. aureus and E.coli as compare with standard drug Streptomycin. Some of the compounds displayed pronounced biological activity. The resulting products were characterized by IR,1H NMR and13 C NMR spectroscopic method.

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New 1,3-benzodioxole derivatives: Synthesis, evaluation of in vitro schistosomicidal activity and ultrastructural analysis

Schistosomiasis is considered a serious public health problem in 78 countries and territories located in Africa, Asia and America and it is estimated in more than 249 million people infected by any of the species of Schistosoma. The exclusive use of praziquantel (PZQ), effective drug against all species of Schistosoma, has been the basis of the development of a possible resistance against the strains of this parasite. In addition, PZQ is not effective against young forms of worms. Thus, there is a need for the development of new drugs with schistosomicidal activity. The objective of this work was to synthesize and to evaluate the therapeutic potential of new benzodioxole derivatives (3?14) candidates for schistosomicidal drugs. All compounds synthesized showed in vitro schistosomicidal activity. The derivative 12 was considered the best compound, since it took 100% of worms to mortality in the first 72 h of exposure at the concentration of 100 muM and 83.3% at the concentration of 50 muM. Furthermore, male and female adult worms, incubated for 24 h with the compound 12 showed tegument damages characterized by extensive desquamation and edema, tuber destruction, bubble formation and exposure of the muscle layer. This compound has a restricted structure, where the thiazolidinone is attached to the 4-position of the 1,3-benzodioxol ring. The structural conformation of derivative 12 was probably responsible for the promising schistosomicidal activity, where the presence of an electron/conformational restriction of the thiazolidine ring, as well as the action of bromine as a bulk substitute, favored an increase in biological activity. In addition, tegumentary changes caused by derivative 12 may also have been responsible for the death of adult worms of Schistosoma mansoni. Therefore, we verified that the results obtained in this study make benzodioxole derivatives possible candidates for prototypes of new schistosomicidal drugs.

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Diastereoselective synthesis of (aryloxy)phosphoramidate prodrugs

The first diastereoselective synthesis of aryloxyphosphoramidate prodrugs of 3?-deoxy-2?,3?-didehydrothymidinemonophosphate (d4TMP) was recently reported. The synthetic approach utilized the chiral auxiliary (S)-4-isopropylthiazolidine-2-thione (2). For this strategy, a stereochemically pure phosphorodiamidate intermediate was needed. The diastereoselective formation of this key compound was investigated by using different phenols and L-alanine methyl or benzyl ester. Generally, the reaction with 3- or 4-substituted phenols led to significantly better diastereoselectivities compared to their 2-substituted counterparts. Moreover, variation of the ester group in the amino acid residue resulted in no significant differences with regard to the obtained diastereoselectivity. From the reported results, a model for the transition state was elaborated. Finally, eight new (S P)-arylphosphoramidates were synthesized with very high diastereoselectivities (up to ? 95 % de) and tested for their anti-HIV potency, showing a tendency for higher antiviral activity from the (S P) diastereomers.

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Extracurricular laboratory:new discovery of 1,1-Dioxo-isothiazolidine

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HYDROXYETHYLAMINE DERIVATIVES FOR THE TREATMENT OF ALZHEIMER’S DISEASE

The present invention relates to novel hydroxyethylamine compounds of formula (I): (I) having Asp2 (-secretase, BACE1 or Memapsin) inhibitory activity, processes for their preparation, to compositions containing them and to their use in the treatment of diseases characterised by elevated-amyloid levels or-amyloid deposits, particularly Alzheimer’s disease.

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Synthesis and Fungicidal Activity of Simple Structural 1,3-Thiazolidine-2-Thione Derivatives

A series of simple structural 1,3-thiazolidine-2-thione derivatives with various substituents on the S-, N-, 4-, and 5-positions was synthesized with high yields from various vicinal amino alcohols via two steps and screened for their antifungal activity. Bioassay results reveal that some thiazolidine-2-thione derivatives show strong antifungal activities against P. capsici, G. zeae, S. sclerotiorum, A. alternata, B. cinerea, or R. solani. The SAR analysis indicates that N-acyl substituted and 4-alkyl substituents can enhance the antifungal activity. Notably, 4-isopropyl-N-propionylthiazoldine-2-thione shows excellent activity against B. cinerea and G. zeae with IC50 values at 3.7 g/mL and 6.5 g/mL, respectively, and 4-isobutyl-N-propionylthiazoldine-2-thione shows remarkable fungicidal activity against R. solani, S. sclerotiorum, and G. zeae with IC50 values at 1.0 g/mL, 12.1 g/mL, and 11.0 g/mL, respectively. GRAPHICAL ABSTRACT.

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Discovery of Thiazolidin-2-one

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Recent developments of coumarin hybrids as anti-fungal agents

Fungi place a huge burden on global healthcare systems attributed to the fact that fungal infections are responsible for the high morbidity and mortality rates in patients who received stem cell transplantation, antineoplastic chemotherapy, organ transplants or suffered Human Immunodeficiency Virus (HIV) infection. Unfortunately, almost none of the representative anti-fungal agents currently used in clinical therapy are ideal in terms of efficacy, anti-fungal spectrum or safety. Moreover, the rapid development of resistance to existing anti-fungal drugs has further aggravated the mortality and spread of fungi, creating an urgent need for novel anti-fungal agents. The broad spectrum of biological activities and successful usage in clinic made coumarins a promising anti-fungal candidate. Furthermore, hybridization of other pharmacophores with coumarin motif may enhance the anti-fungal efficacy, broaden the anti-fungal spectrum and improve the safety profiles. Thus, numerous coumarin hybrids have been assessed for their anti-fungal activities, and some of them showed promising potency and may have a novel mechanism of action. This review aims to outline the recent development of coumarin hybrids as potential anti-fungal agents and summarize their Structure-Activity Relationship (SAR) to provide an insight for rational designs of more active agents.

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Inhibition of transformation in cultured rat tracheal epithelial cells by potential chemopreventive agents

Twenty-eight compounds were screened for chemopreventive activity by using a rat tracheal epithelial cell transformation inhibition assay. In this new assay, chemicals were tested for their ability to inhibit the formation of transformed rat tracheal epithelial cell colonies which arise following exposure to the carcinogen benzo(a)pyrene. The 15 positive compounds were N-acetylcysteine, bismuththiol, calcium glucarate, (±) catechin, diallyl disulfide, glycaric acid, D-glucaro-1,4-lactone, N-(4-hydroxyphenyl)retinamide, D-limonene, mesna, retinoic acid, rutin, quercetin, silymarin, and taurine. In examining the nature of compounds that inhibited rat tracheal epithelial cell transformation, several possible chemopreventive mechanisms appeared to be predominant: compounds that were positive (a) increased glutathione levels or enhanced conjugation; (b) increased cytochrome P-450 activity; (c) displayed nucleophilic activity; or (d) induced differentiation. Thirteen compounds were negative in the rat tracheal epithelial transformation inhibition assay: crocetin, difluoromethylornithine, ellagic acid, esculetin, enoxalone, ibuprofen, levamisole, nordihydroguaiaretic acid, L-2-oxothiazolidine-4-carboxylate, piroxicam, sodium butyrate, D-alpha-tocopherol acetate, and polyethylene glycol 400. It was evident from these results that this assay would not detect compounds that were (a) antipromoting in nature; (b) glutathione inhibitors; (c) differentiation inhibitors; (d) O6-methylguanine inhibitors; (e) organ specific; or (f) inactive. The rat tracheal epithelial cell transformation inhibition assay appeared to identify chemopreventive compounds that act at early stages of the carcinogenic process.

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