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Neglected Tropical Diseases (NTDs) affect more than a billion people worldwide, mainly populations living in poverty conditions. More than 56% of annual NTD deaths are caused by Leishmaniasis, Sleeping sickness, and Chagas disease. For these three diseases, many problems have been observed with the chemotherapeutic drugs commonly used, these being mainly resistance, high toxicity, and low efficacy. In the search for alternative treatments, hybridization is an interesting approach, which generates new molecules by merging two pharmacophores and then looking for improvements in biological activity or reduced compound toxicity. Here, we review various studies that present such hybrid molecules with promising in vitro and in vivo activities against Leishmania and Trypanosoma parasites.

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Background: Diseases caused by microbial infections are very common worldwide. Although the search of innovative antimicrobial agents is the current focus for the researchers, the treatment of infectious diseases remains an important public health issue and a challenging problem in front of medicinal chemist. Methods: A series of 2-(4-hydroxyphenyl)-3-(4-(4-nitrophenyl) thiazol-2-yl)thiazolidin-4-one derivatives (T1-T10) was designed and synthesized. All the titled compounds were evaluated for their antimicrobial potential. Antimicrobial activity was performed by tube dilution methods against Gram negative Escherichia coli MTCC 443 (E. Coli), Gram positive bacteria: Staphylococcus aureus MTCC 3160 (S. aureus) and Bacillus subtilis MTCC 441 (B. Subtilis), and fungal strains: Aspergillus niger MTCC 281 (A. niger) and Candida albicans MTCC 227 (C. albicans). Results: Among the synthesized derivatives, compounds 2, 4 and 10 were found to be most active antimicrobial agents. Conclusion: In conclusion, a series of 2-(phenyl)-3-(4-(phenyl)thiazol-2-yl)thiazolidin-4-ones have been designed and synthesized. All the titled compounds were evaluated for their in vitro antimicrobial activity against five representative microorganisms. The results of antimicrobial study indicated that the presence of nitro and chloro groups in aromatic ring improved antibacterial activity, whereas the presence of hydroxy group improved antifungal activity of substituted 4-thiazolidinone derivatives.

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The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl; or corresponds to a group R5; R2 is hydrogen or C1-4alkyl; R3 is C1-4alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5-or 6-membered heteroaromatic group, or a 8-to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl,-CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; and when R1 is chlorine and p is 1, such R 1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R1 corresponds to R5, p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

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The reaction of 3-substituted 2-(N-cyanoimino)thiazolidine (NCT) derivatives with hydrazine hydrate afforded two types of 1,2,4-triazoles via a selective C2-S or C2-N3 bond fission, in which the selectivity was controlled by the N3-substituent.

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This study is concerned with the synthesis and characterization derivatives of Thiaszolidinones 3a-e. These compounds were synthesized by reacting of thioglycolic acid with the appropriate Schiff base 2a-e, in the presence of dry benzene in moderate yields (69-73%). The structures of Thiaszolidinone were established on the basis of the spectral data like FT-IR, 1H-NMR, 13C-NMR, Gcosy and Mass.

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Reference of 76186-04-4, Because a catalyst decreases the height of the energy barrier, its presence increases the reaction rates of both the forward and the reverse reactions by the same amount.76186-04-4, Name is (S)-4-Isopropylthiazolidine-2-thione, molecular formula is C6H11NS2. In a article,once mentioned of 76186-04-4

Direct anti Glycolate Aldol Reaction of Protected Chiral N-Hydroxyacetyl Thiazolidinethiones with Acetals Catalyzed by a Nickel(II) Complex

The direct and stereocontrolled addition of (S)-4-isopropyl-N-(2-pivaloyloxyacetyl)-1,3-thiazolidine-2-thione to dialkyl acetals of aromatic and alpha,beta-unsaturated aldehydes catalyzed by 2.5?5 mol-% of a nickel(II) complex permits the synthesis of diastereomerically pure and fully protected anti aldol adducts in good to high yields. The catalytic species is formed in situ from commercially available and easy to handle (Me3P)2NiCl2, which makes this reaction a direct, catalytic, and experimentally simple approach to the asymmetric anti glycolate aldol reaction.

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Quantum chemical studies for some thiazolidinone derivatives using density functional theory

B3LYP/6-311G++(d, p) calculations have been carried out to study the structural and chemical properties of thioazilinone derivatives. The optimized molecular geometry of these derivative molecules are compared with the synthesized results of Mushtaque et al. The calculated results show that the density functional theory (DFT) can well reproduce the structure of the title compounds. Highest occupied-Lowest unoccupied molecular orbital (HOMO?LUMO) gap of the derivatives molecules are comparatively smaller then bare thiazolidinone. Natural bond orbital analysis for these title molecules shows strong delocalization of lone pair electrons from N, S, and O to the chemical bonds associated with central thiazolidinonering. The infrared intensites are calculated to compare with the FT-IR observation reported by Mushtaque et al. The experimental UV-Vis spectrum of present derivatives have been recorded and compared with calculated time dependent density functional (TDDFT) approach. The qualitative measures of chemical activeness of molecules have been presented in terms molecular electrostatic potential (MEP).

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COMPOSITION FOR MAINTAINING CHROMOSOMAL STABILITY OF PLURIPOTENT STEM CELLS, CONTAINING SMALL-MOLECULE COMPOUND

The present invention relates to a composition for maintaining the chromosomal stability of pluripotent stem cells, which contains a small-molecule compound, and more particularly, to a composition for maintaining the chromosomal stability of induced pluripotent stem cells, which contains a ROCK inhibitor, a MEK inhibitor, an ALK5 inhibitor or an antioxidant, which is capable of inhibiting chromosomal structural and numerical mutations or DNA damage during induction of induced pluripotent stem cell and the subsequent culture of the cells. The small-molecule compound-containing composition for maintaining the chromosomal stability of induced pluripotent stem cells increases the reprogramming rate and efficiency during production of induced pluripotent stem cells and exhibits excellent effects on the inhibition of chromosomal structural and numerical mutations or DNA damage. Thus, the composition of the present invention is very useful for the development of induced pluripotent stem cell therapeutic agents having excellent chromosomal stability.

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MUSCARINIC AGONISTS

The present invention relates to compounds of Formula (I): which are agonists of the M-1 muscarinic receptor.

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Dietary antioxidants prevent alcohol-induced ciliary dysfunction

Previously we have shown that chronic alcohol intake causes alcohol-induced ciliary dysfunction (AICD), leading to non-responsive airway cilia. AICD likely occurs through the downregulation of nitric oxide (NO) and cyclic nucleotide-dependent kinases, protein kinase G (PKG) and protein kinase A (PKA). Studies by others have shown that dietary supplementation with the antioxidants N-acetylcysteine (NAC) and procysteine prevent other alcohol-induced lung complications. This led us to hypothesize that dietary supplementation with NAC or procysteine prevents AICD. To test this hypothesis, C57BL/6 mice drank an alcohol/water solution (20% w/v) ad libitum for 6 weeks and were concurrently fed dietary supplements of either NAC or procysteine. Ciliary beat frequency (CBF) was measured in mice tracheas, and PKG/PKA responsiveness to beta-agonists and NOx levels were measured from bronchoalveolar lavage (BAL) fluid. Long-term alcohol drinking reduced CBF, PKG and PKA responsiveness to beta-agonists, and lung NOx levels in BAL fluid. In contrast, alcohol-drinking mice fed NAC or procysteine sustained ciliary function and PKG and PKA responsiveness to beta-agonists. However, BAL NO levels remained low despite antioxidant supplementation. We also determined that removal of alcohol from the drinking water for as little as 1 week restored ciliary function, but not PKG and PKA responsiveness to beta-agonists. We conclude that dietary supplementation with NAC or procysteine protects against AICD. In addition, alcohol removal for 1 week restores cilia function independent of PKG and PKA activity. Our findings provide a rationale for the use of antioxidants to prevent damage to airway mucociliary functions in chronic alcohol-drinking individuals.

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