- Antileishmanial activity evaluation of thiazolidine-2,4-dione against Leishmania infantum and Leishmania braziliensis
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Leishmaniasis is responsible for approximately 65,000 annual deaths. Despite the mortality data, drugs available for the treatment of patients are insufficient and have moderate therapeutic efficacy in addition to serious adverse effects, which makes the development of new drugs urgent. To achieve this goal, the integration of kinetic and DSF assays against parasitic validated targets, along with phenotypic assays, can help the identification and optimization of bioactive compounds. Pteridine reductase 1 (PTR1), a validated target in Leishmania sp., is responsible for the reduction of folate and biopterin to tetrahydrofolate and tetrahydrobiopterin, respectively, both of which are essential for cell growth. In addition to the in vitro evaluation of 16 thiazolidine-2,4-dione derivatives against Leishmania major PTR1 (LmPTR1), using the differential scanning fluorimetry (ThermoFluor), phenotypic assays were employed to evaluate the compound effect over Leishmania braziliensis (MHOM/BR/75/M2903) and Leishmania infantum (MHOM/BR/74/PP75) promastigotes viability. The ThermoFluor results show that thiazolidine-2,4-dione derivatives have micromolar affinity to the target and equivalent activity on Leishmania cells. 2b is the most potent compound against L. infantum (EC50 = 23.45 ± 4.54 μM), whereas 2a is the most potent against L. braziliensis (EC50 = 44.16 ± 5.77 μM). This result suggests that lipophilic substituents on either—meta and/or—para positions of the benzylidene ring increase the potency against L. infantum. On the other hand, compound 2c (CE50 = 49.22 ± 7.71 μM) presented the highest selectivity index.
- Castilho, Marcelo Santos,Froes, Thamires Quadros,Júnior, David Bacelar Costa,Leite, Franco Henrique Andrade,Moreira, Paulo Otávio Louren?o,Neri, Flávio Simas Moreira,Teixeira-Neto, Rafael Gon?alves,da Silva, Priscila Brand?o Gomes,de Albuquerque, Jullianna Ferreira Cavalcanti,de Pilla Varotti, Fernando,do Egito, Micalyne Soares
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- Design and synthesis of 4′-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs as bacterial peptide deformylase inhibitors
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Herein, we report the synthesis and screening of 4′-((5-benzylidene-2,4-dioxothiazolidin-3-yl)methyl)biphenyl-2-carbonitrile analogs 11(a–j) as bacterial peptide deformylase (PDF) enzyme inhibitors. The compounds 11b (IC50 value?=?139.28?μm), 11g (IC50 value?=?136.18?μm), and 11h (IC50 value?=?131.65?μm) had shown good PDF inhibition activity. The compounds 11b (MIC range?=?103.36–167.26?μg/mL), 11g (MIC range?=?93.75–145.67?μg/mL), and 11h (MIC range?=?63.61–126.63?μg/mL) had also shown potent antibacterial activity when compared with standard ampicillin (MIC range?=?100.00–250.00?μg/mL). Thus, the active derivatives were not only PDF inhibitors but also efficient antibacterial agents. To gain more insight on the binding mode of the compounds with PDF enzyme, the synthesized compounds 11(a–j) were docked against PDF enzyme of Escherichia coli and compounds exhibited good binding properties. The results suggest that this class of compounds has potential for development and use in future as antibacterial drugs.
- Khan, Firoz A. Kalam,Patil, Rajendra H.,Shinde, Devanand B.,Sangshetti, Jaiprakash N.
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p. 938 - 944
(2016/11/11)
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- New compounds having skin whitening, antioxidant and PPAR activity, and medical use thereof
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PURPOSE: A novel compound with skin whitening, antioxidation, and PPAR activation effects, and a medical use thereof are provided to be used for a pharmaceutical composition or a cosmetic product. CONSTITUTION: A compound is denoted by chemical formula 1. A skin whitening composition contains the compound as an active ingredient. An antioxidative composition for preventing or treating oxidative diseases contains the compound of chemical formula 1 as an active ingredient. The oxidative diseases are selected among skin aging, pigmentation, wrinkling, psoriasis, or eczema. The composition prevents or treats diseases which are regulated by PPAR(peroxisome proliferator-activated receptor) activity. The PPAR includes PPAR alpha or PPAR gamma.
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Paragraph 0122; 0138
(2017/04/14)
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- NOVEL COMPOUND HAVING SKIN-WHITENING, ANTI-OXIDIZING AND PPAR ACTIVITIES AND MEDICAL USE THEREFOR
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Provided are a novel compound having skin-whitening, anti-oxidizing and PPAR activities and a medical use thereof, and the compound has skin-whitening activities for the suppression of tyrosinase, and accordingly, is useful for use in skin-whitening pharmaceutical composition or cosmetic products; has anti-oxidant activities, and accordingly, is useful for the prevention and treatment of skin-aging; and has PPAR activities, and in particular, PPARα and PPARγ activities, and accordingly, is useful for use in pharmaceutical compositions or health foods which are effective for the prevention and treatment of obesity, metabolic disease, or cardiovascular disease.
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Paragraph 0122-0123; 0131
(2014/02/16)
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- Privileged scaffolds or promiscuous binders: A comparative study on rhodanines and related heterocycles in medicinal chemistry
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Rhodanines and related five-membered heterocycles with multiple heteroatoms have recently gained a reputation of being unselective compounds that appear as "frequent hitters" in screening campaigns and therefore have little value in drug discovery. However, this judgment appears to be based mostly on anecdotal evidence. Having identified various rhodanines and related compounds in screening campaigns, we decided to perform a systematic study on their promiscuity. An amount of 163 rhodanines, hydantoins, thiohydantoins, and thiazolidinediones were synthesized and tested against several targets. The compounds were also characterized with respect to aggregation and electrophilic reactivity, and the binding modes of rhodanines and related compounds in published X-ray cocrystal structures were analyzed. The results indicate that the exocyclic, double bonded sulfur atom in rhodanines and thiohydantoins, in addition to other structural features, offers a particularly high density of interaction sites for polar interactions and hydrogen bonds. This causes a promiscuous behavior at concentrations in the "screening range" but should not be regarded as a general knockout criterion that excludes such screening hits from further development. It is suggested that special criteria for target affinity and selectivity are applied to these classes of compounds and that their exceptional and potentially valuable biomolecular binding properties are consequently exploited in a useful way.
- Mendgen, Thomas,Steuer, Christian,Klein, Christian D.
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supporting information; experimental part
p. 743 - 753
(2012/03/11)
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- Design and synthesis of 5-(substituted benzylidene)thiazolidine-2,4-dione derivatives as novel tyrosinase inhibitors
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In continuing our search for novel tyrosinase inhibitors, a series of 5-(substituted benzylidene)thiazolidine-2,4-diones were rationally designed and synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. Twelve target c
- Ha, Young Mi,Park, Yun Jung,Kim, Jin-Ah,Park, Daeui,Park, Ji Young,Lee, Hye Jin,Lee, Ji Yeon,Moon, Hyung Ryong,Chung, Hae Young
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experimental part
p. 245 - 252
(2012/04/10)
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- Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, and PIM-3 protein kinases
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Novel substituted benzylidene-1,3-thiazolidine-2,4-diones (TZDs) have been identified as potent and highly selective inhibitors of the PIM kinases. The synthesis and SAR of these compounds are described, along with X-ray crystallographic, anti-proliferati
- Dakin, Les A.,Block, Michael H.,Chen, Huawei,Code, Erin,Dowling, James E.,Feng, Xiaomei,Ferguson, Andrew D.,Green, Isabelle,Hird, Alexander W.,Howard, Tina,Keeton, Erika K.,Lamb, Michelle L.,Lyne, Paul D.,Pollard, Hannah,Read, Jon,Wu, Allan J.,Zhang, Tao,Zheng, Xiaolan
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scheme or table
p. 4599 - 4604
(2012/08/07)
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- CHEMICAL COMPOUNDS 251
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The invention relates to chemical compounds of formula (I), and salts thereof. In some embodiments, the invention relates to inhibitors or modulators of PIM-1 and/or PIM-2, and/or PIM-3 protein kinase activity or enzyme function. In still further embodiments, the invention relates to pharmaceutical compositions comprising compounds disclosed herein, and their use in the prevention and treatment of PIM kinase related conditions and diseases, preferably cancer.
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Page/Page column 38
(2011/10/02)
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- Dicationic ionic liquid mediated synthesis of 5-arylidine-2,4- thiazolidinediones
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An efficient synthesis of 5-arylidine-2,4-thiazolidinediones has been developed using dicationic ionic liquid as green medium and catalyst. This method performed well for the condensation of both aryl as well as heteryl aldehydes with 2,4-thiazolidinedion
- Jawale, Dhanaji V.,Pratap, Umesh R.,Lingampalle, Dinesh L.,Mane, Ramrao A
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experimental part
p. 942 - 946
(2012/01/04)
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- Synthesis of 5-arylidene-2,4-thiazolidinediones by Knoevenagel condensation catalyzed by baker's yeast
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An ecofriendly baker's yeast catalyzed Knoevenagel condensation of aromatic aldehydes and active methylene compounds has been performed. The developed protocol has been found to be applicable for obtaining 5-arylidene-2,4- thiazolidinediones, the precursors of hypoglycemic agents. The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2011.
- Pratap, Umesh R.,Jawale, Dhanaji V.,Waghmare, Rahul A.,Lingampalle, Dinesh L.,Mane, Ramrao A.
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experimental part
p. 49 - 51
(2011/04/14)
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- Synthesis and structure of new 5-(arylidene)-3-(4-methylbenzoyl) thiazolidine-2,4-diones
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(Chemical Equation Presented) The derivatives of 5-substituted-2,4- thiazolidinedione have a broad spectrum of biological activities. In this article, new 5-(arylidene)-3-(4-methylbenzoyl)thiayolidine-2,4-diones 3a-k, with arylidene groups such as 4-pheny
- Popov-Pergal, Katarina M.,Poleti, Dejan,Rancic, Milica P.,Meden, Antun,Pergal, Marija V.
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scheme or table
p. 224 - 228
(2010/04/27)
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- Discovery of (Z)-5-(4-methoxybenzylidene)thiazolidine-2,4-dione, a readily available and orally active glitazone for the treatment of concanavalin A-induced acute liver injury of BALB/c mice
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A large amount of evidence suggests that monocytes/macrophages infiltration is implicated in a variety of inflammatory diseases including acute liver injury. Monocyte chemoattractant protein 1 (MCP-1) plays a crucial role in the process of macrophages recruitment. We herein presented a small-molecule library and a feasible quick screening method of evaluating potency of inhibition of chemotaxis of RAW264.7 cells stimulated by MCP-1. Fifty-three small molecules were synthesized and screened, and four compounds (2g, 2h, 4f, and 6h) showed inhibitory effects with IC50 values range from 0.72 to 20.47 μM, with compound 4f being the most efficient. Further in vivo studies demonstrated that oral administration of 2g, 2h, 4f, or 6h decreases, most significantly for 4f, the serum levels of alanine aminotransaminase (ALT) and asparate aminotransaminase (AST) in ConA-induced acute livery injury BALB/c mice. Histopathological evaluation liver sections confirmed 4f as a potent, orally active compound for hepatoprotective effects against ConA-induced acute liver injury in BALB/c mice.
- Luo, Youfu,Ma, Liang,Zheng, Hao,Chen, Lijuan,Li, Rui,He, Chunmei,Yang, Shengyong,Ye, Xia,Chen, Zhizhi,Li, Zicheng,Gao, Yan,Han, Jing,He, Gu,Yang, Li,Wei, Yuquan
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experimental part
p. 273 - 281
(2010/05/02)
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- Synthesis and in vivo antidiabetic activity of novel dispiropyrrolidines through [3 + 2] cycloaddition reactions with thiazolidinedione and rhodanine derivatives
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The synthesis of a series of novel dispiropyrrolidines has been accomplished by 1,3-dipolar cycloaddition reaction with 5-arylidene-1,3-thiazolidine-2,4-dione and 5-arylidene-4-thioxo-1,3-thiazolidine-2-one derivatives as dipolarophiles. The structure and stereochemistry of the cycloadduct have been established by single crystal X-ray structure and spectroscopic techniques. Molecular docking studies were performed on 1FM9 protein. The synthesized compounds were screened for their antidiabetic activity on male Wistar rats.
- Murugan, Ramalingam,Anbazhagan,Sriman Narayanan
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scheme or table
p. 3272 - 3279
(2009/10/17)
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- Synthesis of some new pyrazolo[3,4-d]pyrimidines and thiazolo [4,5-d]pyrimidines and evaluation of their antimicrobial activities
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The desired fused ring system 3-isopropyl-4-aryl-1,4,5,7-tetrahydro- pyrazolo[3,4-d]pyrimidine-6-thiones 4a-d were synthesized by the reaction of 5-isopropyl-2,4-dihydro-3-pyrazolone 1, thiourea and different aromatic aldehydes, while 7-aryl-5-thioxo-4,5,
- Akbari,Tala,Dhaduk,Joshi,Mehta,Pathak
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experimental part
p. 1471 - 1477
(2009/05/07)
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- Rhodanine derivatives as novel inhibitors of PDE4
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The discovery, synthesis and in vitro activity of a novel series of rhodanine based phosphodiesterase-4 (PDE4) inhibitors is described. Structure-activity relationship studies directed toward improving potency led to the development of submicromolar inhibitors 2n and 3i (IC50 = 0.89 & 0.74 μM). The replacement of rhodanine with structurally related heterocycles was also investigated and led to the synthesis of pseudothiohydantoin 7 (IC50 = 0.31 μM).
- Irvine, Mark W.,Patrick, Graham L.,Kewney, Justin,Hastings, Stuart F.,MacKenzie, Simon J.
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p. 2032 - 2037
(2008/12/21)
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- Synthesis of 5-arylidene-3-(4′-bromobenzyl)thiazolidine-2,4-diones
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Potential antihistamines 5-arylidene-3-(4′-bromobenzyl)thiazolidine- 2,4-diones were synthesized using 5-arylidenethiazolidine-2,4-dione potassium salt and 4-bromobenzyl bromide in dry acetone. The log P values are given for all the synthesized compounds.
- Popov-Pergal,Pergal,Csanadi,Djokovic
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p. 1529 - 1533
(2007/10/03)
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- A convenient synthesis of 5-benzylidenethiazolidine-2, 4-diones under microwave irradiation without solvent
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A series of 5-benzylidenethiazolidine-2,4-diones was synthesised by the Knoevenagel condensation of aromatic aldehydes with thiazolidine-2,4-dione in the presence of catalytic amounts of piperidine and acetic acid under microwave irradiation without solvent in good yields.
- Yang, De-Hong,Chen, Zhen-Chu,Chen, Song-Ying,Zheng, Qin-Guo
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p. 330 - 331
(2007/10/03)
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- CONDENSATION OF 2,4-DIOXOTETRAHYDRO-1,3-THIAZOLE WITH AROMATIC ALDEHYDES
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It was shown that the morpholine catalyzed condensation of 2,4-dioxotetrahydro-1,3-thiazole with aromatic aldehydes is a convenient preparative method for the preparation of 5-arylidene-2,4-dioxotetrahydro-1,3-thiazoles.The pesticidal activity of the synt
- Popov-Pergal, K.,Cekovic, Z.,Pergal, M.
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p. 1958 - 1962
(2007/10/02)
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