- Design and synthesis of amino acid derivatives of substituted benzimidazoles and pyrazoles as Sirt1 inhibitors
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Owing to its presence in several biological processes, Sirt1 acts as a potential therapeutic target for many diseases. Here, we report the structure-based designing and synthesis of two distinct series of novel Sirt1 inhibitors, benzimidazole mono-peptide
- Asthana, Shailendra,Banerjee, Sanjay K.,Kumar, Vasantha,Paramesha, Bugga,Poojary, Boja,Purushotham, Nikil,Singh, Mrityunjay,Wakode, Sharad
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p. 3809 - 3827
(2022/02/16)
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- 5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl)alkancarboxylic Acids as Antimicrobial Agents: Synthesis, biological evaluation, and molecular docking studies
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Background: Infectious diseases symbolize a global consequential strain on public health security and impact on the socio-economic stability all over the world. The increasing resistance to the current antimicrobial treatment has resulted in crucial need for the discovery and development of novel entity for the infectious treatment with different modes of action that could target both sensitive and resistant strains. Methods: Compounds were synthesized using classical methods of organic synthesis. Results: All 20 synthesized compounds showed antibacterial activity against eight Gram-positive and Gram-negative bacterial species. It should be mentioned that all compounds exhibited better antibacterial potency than ampicillin against all bacteria tested. Furthermore, 18 compounds appeared to be more potent than streptomycin against Staphylococcus aureus, Enterobacter cloacae, Pseudomonas aeruginosa, Listeria monocytogenes, and Escherichia coli. Three the most active compounds 4h, 5b, and 5g appeared to be more potent against MRSA than ampicillin, while streptomycin did not show any bactericidal activity. All three compounds displayed better activity also against resistant strains P. aeruginosa and E. coli than ampicillin. Furthermore, all compounds were able to inhibit biofilm formation 2- to 4-times more than both reference drugs. Compounds were evaluated also for their antifungal activity against eight species. The evaluation revealed that all compounds exhibited antifungal activity better than the reference drugs bifonazole and ketoconazole. Molecular docking studies on antibacterial and antifungal targets were performed in order to elucidate the mechanism of antibacterial activity of synthesized compounds. Conclusion: All tested compounds showed good antibacterial and antifungal activity better than that of reference drugs and three the most active compounds could consider as lead compounds for the development of new more potent agents.
- Ciric, Ana,Geronikaki, Athina,Glamoclija, Jasmina,Horishny, Volodymyr,Kartsev, Victor,Matiychuk, Vasyl,Petrou, Anthi,Sokovic, Marina
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- Synthesis and evaluation of some novel N-substituted rhodanines for their anticancer activity
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Novel N-substituted rhodanines 2a-g were synthesized by conventional and microwave-assisted methods and tested for their anticancer activity. Structure-activity relationship of the synthesized rhodanine 2a-g as antiproliferative agents was investigated. The results revealed that all the seven compounds showed potent antiproliferative activity in a concentration-dependent manner on leukemic cell line K562. Among the tested compounds, 2b was found to be more potent when compared by trypan blue and MTT assay. IC50 values of 2b using trypan blue and MTT assay were found to be 11.1 and 20.3 μg/ml, respectively. A dose-dependent increase in the LDH release was also observed upon treatment with 2a-g. Cell cycle analysis revealed that 2b affects DNA replication and leads to accumulation of cells in G0 and decline of G2/M, G1 and S phases which indicates apoptosis. The selective cytotoxic activity against human chronic myelogenous cell line (K562), via apoptosis, suggests that compound 2b is a promising scaffold for the development of novel anticancer drug.
- Ali Muhammad, Sulaiman,Ravi, Subban,Thangamani, Arumugam
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p. 994 - 1004
(2016/04/20)
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- Synthesis and antimicrobial evaluation of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety
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Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by 1H NMR, 13C NMR, infrared and mass spectroscopy.
- Li, Chao,Liu, Jia-Chun,Li, Ya-Ru,Gou, Cheng,Zhang, Mei-Ling,Liu, Hong-Yan,Li, Xiao-Zhen,Zheng, Chang-Ji,Piao, Hu-Ri
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supporting information
p. 3052 - 3056
(2015/06/22)
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- Discovery of the first potent and selective Mycobacterium tuberculosis Zmp1 inhibitor
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The Mycobacterium tuberculosis extracellular zinc metalloprotease 1 (Zmp1) has been proposed to play a key role in phagosome maturation and to enhance the survival of Mycobacterium tuberculosis in the host. Consequently, small molecule inhibitors of Zmp1
- Mori, Mattia,Moraca, Francesca,Deodato, Davide,Ferraris, Davide M.,Selchow, Petra,Sander, Peter,Rizzi, Menico,Botta, Maurizio
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supporting information
p. 2508 - 2511
(2014/05/20)
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- Novel arylhydrazone derivatives bearing a rhodanine moiety: Synthesis and evaluation of their antibacterial activities
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A series of arylhydrazone derivatives bearing a rhodanine moiety have been synthesized, characterized, and evaluated as antibacterial agents. Some of these compounds showed potent antibacterial activities against several different strains of Gram-positive bacteria, including multidrug-resistant clinical isolates. Of the compounds tested, IIk and IIIk were identified as the most effective, with minimum inhibitory concentration values of 2-4 μg/mL against multidrug-resistant Gram-positive organisms, including methicillin-resistant and quinolone-resistant Staphylococcus aureus. None of the compounds exhibited any activity against the Gram-negative bacteria Escherichia coli 1356 at 64 μg/mL.
- Li, Wei,Zheng, Chang-Ji,Sun, Liang-Peng,Song, Ming-Xia,Wu, Yan,Li, Yin-Jing,Liu, Yi,Piao, Hu-Ri
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p. 852 - 861
(2014/08/05)
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- Synthesis and biological evaluation of (E)-1-(substituted)-3-phenylprop-2-en-1-ones bearing rhodanines as potent anti-microbial agents
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Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC=1-8μg/mL) against multi-drug-r
- Song, Ming-Xia,Deng, Xian-Qing,Li, Ya-Ru,Zheng, Chang-Ji,Hong, Lan,Piao, Hu-Ri
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p. 647 - 653
(2015/02/18)
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- Thiazolidinone-peptide hybrids as dengue virus protease inhibitors with antiviral activity in cell culture
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The protease of dengue virus is a promising target for antiviral drug discovery. We here report a new generation of peptide-hybrid inhibitors of dengue protease that incorporate N-substituted 5-arylidenethiazolidinone heterocycles (rhodanines and thiazolidinediones) as N-terminal capping groups of the peptide moiety. The compounds were extensively characterized with respect to inhibition of various proteases, inhibition mechanisms, membrane permeability, antiviral activity, and cytotoxicity in cell culture. A sulfur/oxygen exchange in position 2 of the capping heterocycle (thiazolidinedione-capped vs rhodanine-capped peptide hybrids) has a significant effect on these properties and activities. The most promising in vitro affinities were observed for thiazolidinedione-based peptide hybrids containing hydrophobic groups with Ki values between 1.5 and 1.8 μM and competitive inhibition mechanisms. Rhodanine-capped peptide hybrids with hydrophobic substituents have, in correlation with their membrane permeability, a more pronounced antiviral activity in cell culture than the thiazolidinediones.
- Nitsche, Christoph,Schreier, Verena N.,Behnam, Mira A. M.,Kumar, Anil,Bartenschlager, Ralf,Klein, Christian D.
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p. 8389 - 8403
(2013/12/04)
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- Synthesis and antimicrobial evaluation of L-phenylalanine-derived C5-substituted rhodanine and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone
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Four novel series of compounds, including the l-phenylalanine-derived C5-substituted rhodanine (6a-q, 7a-j) and chalcone derivatives containing thiobarbituric acid or 2-thioxo-4-thiazolidinone (9a-e, 11a-e) have been designed, synthesized, characterized, and evaluated for their antibacterial activity. Some of these compounds showed significant antibacterial activity against Gram-positive bacterias, especially against the strains of multidrug-resistant clinical isolates, among which compounds 6c-e, 6g, 6i, 6j and 6q exhibiting high levels of antimicrobial activity against Staphylococcus aureus RN4220 with minimum inhibitory concentration (MIC) values of 2 μg/mL. Compound 6q showed the most potent activity of all of the compounds against all of the test multidrug-resistant clinical isolates tested. Unfortunately, however, none of the compounds were active against Gram-negative bacteria at 64 μg/mL.
- Zheng, Chang-Ji,Song, Ming-Xia,Wu, Yan,Sun, Liang-Peng,Li, Yin-Jing,Piao, Hu-Ri,Jin, Xin,Yu, Li-Jun
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p. 203 - 209,7
(2012/12/12)
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- BIARYLRHODANINE AND PYRIDYLRHODANINE COMPOUNDS AND THEIR USE
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The present invention pertains generally to the field of therapeutic compounds, and more specifically to compounds related to rhodanine, which compounds are inter alia inhibitors and/or binders of antiapoptotic/pro-survival Bcl-2 proteins such as Bcl-XL and/or Mcl-1. More specifically, the present invention is concerned with Rhodanine- based Pan-Bcl-2 inhibitors and Mcl-1 -specific inhibitors as anti-cancer compounds. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and invivo, to inhibit and/or bind Bcl-2 proteins such as Bcl-XL and/or Mcl-1, and in the treatment of diseases and conditions that are mediated by Bcl-2 proteins, that are ameliorated by the inhibition of Bcl-2 protein function (such as Bcl-XL and/or Mcl-1 ) including proliferative conditions such as cancer, optionally in combination with another agent.
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Page/Page column 81
(2010/04/06)
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- Structural insights into the design of small molecule inhibitors that selectively antagonize Mcl-1
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The screening of a small focused library of rhodanine derivatives as inhibitors of Bcl-2 proteins led to the discovery of two structurally related compounds with different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent NMR studies with mutant proteins and in silico docking studies provide a possible rationale for the observed specificity.
- Bernardo, Paul H.,Sivaraman, Thirunavukkarasu,Wan, Kah-Fei,Xu, Jin,Krishnamoorthy, Janarthanan,Sons, Chun Meng,Tian, Liming,Chin, Jasmine S. F.,Lim, Diane S. W.,Mok, Henry Y. K.,Yu, Victor C.,Tong, Joo Chuan,Chai, Christina L. L.
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supporting information; experimental part
p. 2314 - 2318
(2010/08/06)
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- The synthesis of phenylalanine-derived C5-substituted rhodanines and their activity against selected methicillin-resistant Staphylococcus aureus (MRSA) strains
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A series of rhodanine compounds containing various substituents at the N3- and C5-positions were synthesized and their in vitro activity against a panel of clinically relevant MRSA strains was determined. The anti-MRSA activity of compounds 21 (MIC = 3.9
- Hardej, Diane,Ashby Jr., Charles R.,Khadtare, Nikhil S.,Kulkarni, Shridhar S.,Singh, Satyakam,Talele, Tanaji T.
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experimental part
p. 5827 - 5832
(2011/02/22)
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- THERAPEUTIC COMPOUNDS
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The invention provides a compound of formula I: wherein R4, R5 and R6 have any of the values described herein or a salt thereof, as well as synthetic processes and intermediates useful for preparing such compounds. The com
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Page/Page column 31
(2009/06/27)
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- Development of dimeric modulators for anti-apoptotic Bcl-2 proteins
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Bcl-2 family proteins can be classified into two subfamilies-anti-apoptotic members and pro-apoptotic members. Mechanistically, these two subfamilies can antagonize each other through heterodimerization while homodimerization has been proposed for each su
- Wang, Liangyou,Kong, Fansen,Kokoski, Candis L.,Andrews, David W.,Xing, Chengguo
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p. 236 - 240
(2008/09/17)
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- Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1
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A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were synthesized and their binding interactions with Bcl-2, Bcl-XL, and Bcl-w were evaluated. It was found that modification of BHI-1 resulted in varied binding profiles am
- Xing, Chengguo,Wang, Liangyou,Tang, XiaoHu,Sham, Yuk Y.
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p. 2167 - 2176
(2008/02/01)
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