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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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Quinuclidine – Wikipedia,
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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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Quinuclidine – Wikipedia,
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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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Quinuclidine – Wikipedia,
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Multi-target compounds acting in cancer progression: Focus on thiosemicarbazone, thiazole and thiazolidinone analogues

Currently, cancer and its progression to metastasis result in a large number of deaths. The lack of new drugs, appropriate clinical trials for metastasis preventive drugs and incomplete understanding of the molecular machinery are the major obstacles in metastasis prevention and treatment. On the other hand, thiosemicarbazones and their bioisosteres, thiazole and thiazolidinone are recurring in a wide range of biologically active compounds that reach different targets within tumor context and represent a promising start point to access potential candidates in metastatic cancer. Therefore, the search for new lead compounds showing highest anticancer potency and less adverse effects is the major challenger in drug discovery. The search was based from 1994 to 2018, focusing on thiosemicarbazone, thiazole and thiazolidinone cores that allowed us to discuss how the three multi-target motifs have been used for the target-based design and development of anticancer agents. In the lasts years, thiosemicarbazone, thiazole, and thiazolidinone cores are recurrent in many approaches for cancer therapy. In our search, it was verified that due to its biodiversity and versatility the anticancer potential of such structures has been assigned to distinct mechanisms reinforcing the value of these cores in the anticancer drug development. The present article aims point out the current application of thiosemicarbazone, thiazole and thiazolidinone cores in the design of anticancer agents within tumor progression, acting via varied targets such as cathepsins, NDRG1 gene and kinases, showing in vitro tests, in vivo tests and clinical trials. In our search it was possible to verify that thiazole is the most studied and the most important of the three structures. Therefore, we hope to provide new insights and valuable inspiration in the research of new drugs and development and contribute to the management of cancer.

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Liquid phase parallel synthesis of chemical libraries

This invention features methods of biphasic synthesis for synthesizing combinatorial libraries and combinatorial libraries of chemical compounds utilizing the template, and combinatorial libraries of chemical compounds formed by the methods of this invention.

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Quinuclidine – Wikipedia,
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Bis(benzofuran?thiazolidinone)s and bis(benzofuran?thiazinanone)s as inhibiting agents for chikungunya virus

There are currently still no approved antiviral drugs to treat or prevent chikungunya virus (CHIKV) infections despite the fact that this arbovirus continues to cause outbreaks in Africa, Asia, and South- and Central-America. Thus 20 new conjugated compounds in the families of bis(benzofuran?1,3-thiazolidin-4-one)s and bis(benzofuran?1,3-thiazinan-4-one)s were designed based on the structural features of suramin. These new compounds were synthesized by chemical methods and their structures were confirmed spectroscopically. In CPE reduction assays, six of these new bis-conjugates inhibited CHIKV replication in Vero E6 cells with EC50 in the range of 1.9?2.7 muM and selectivity index values of ?75 or higher. These results and compounds provide a starting point for further optimization, design, and synthesis of new antiviral agents for this (re)emerging disease.

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A concise synthesis of mono- and polysubstituted and diversely N-function-alized isoindolinones and isoquinolones

A variety of differently substituted and diversely N-(sul-fanyl) hydroxyalkyl functionalized isoindolinones and isoquinolones have been obtained by anionic cyclization of cyclic bromobenzyl or bromophenethylcarbamates and thiocarbamates. Thieme Stuttgart.

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Synthesis, characterization, antibacterial and antiepileptic studies of some novel thiazolidinone derivatives

In the quest of finding new drug leads with potential antibacterial and antiepileptic activities, synthesis of thiazolidinone derivatives 6(a?c) is reported which are obtained from 5-(4-chlorobenzylidine)-3-[4-(7-chloroquinoline-4-ylamino]propyl)-2-imino-thiazolidin-4-one derivatives by applying appropriate synthetic route. These compounds 6(a?c) were evaluated for antibacterial and antiepileptic activities. Compound 6a having good lipophilicity is found to be most active.

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Quinuclidine – Wikipedia,
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A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.

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Reference:
Quinuclidine – Wikipedia,
Quinuclidine | C7H366N | ChemSpider