- Design, synthesis and redox properties of two ferrocene-containing iron chelators
-
Two ferrocene-containing iron(III) chelators were synthesized from desferrioxamine B and kojic acid and their electronic absorption and electrochemical properties were studied in acetonitrile in the absence and presence of ferric ions. The results show a
- Moggia, Fabrice,Brisset, Hugues,Fages, Frédéric,Chaix, Carole,Mandrand, Bernard,Dias, Marylène,Levillain, Eric
-
-
Read Online
- Molecular dynamics simulation and 3D-pharmacophore analysis of new quinoline-based analogues with dual potential against EGFR and VEGFR-2
-
Epidermal growth factor and vascular endothelial growth factor-2 are important targets of tyrosine kinase for the treatment of various cancerous diseases. Combination of inhibition of both targets to produce synergy in the signal pathway is a critical approach to identify novel tyrosine kinase inhibitors. In this study, a series of new compounds derived from the 4-aminoquinoline as dual inhibitors were synthesized. The obtained results of cytotoxicity assay against human carcinoma cell lines indicated 0.8 μM for 4c against A549 showing its high efficiency in comparison to erlotinib. Pharmacophore modeling as a structure-based method was investigated on dual inhibitors and 4c which was compared with co-crystallized in the active site of EGFR and VEGFR-2. They have shown the same binding orientation as vandetanib, erlotinib and sorafenib. Molecular dynamics simulation results approved that Met769, Lys721, Asp1046, and Lys868 are key residues in two binding sites for dual activity. Ala1050 and Pro968 were identified as new amino acid interaction sites for dual inhibition. 4c showed more favorable stability than vandetanib in VEGFR-2 receptor for a 50 ns dynamic simulation. The high correlation between essential pharmacophoric features of designed compounds and lead inhibitors interactions provided a deeper insight into the structural basis of 4-aminoquinoline inhibition.
- Fayyazi, Neda,Fassihi, Afshin,Esmaeili, Somayeh,Taheri, Salman,Ghasemi, Jahan B.,Saghaie, Lotfollah
-
-
- Stilbene-like compound, and preparation method and application thereof
-
The invention discloses a stilbene-like compound. The stilbene-like compound has a structure as shown in a general formula which is any one selected from the group consisting of formulas which are described in the specification. The invention also disclos
- -
-
Paragraph 0031; 0034; 0035; 0036; 0055; 0058; 0059; 0060
(2019/04/26)
-
- COMPOSITIONS AND METHODS FOR INHIBITING INFLUENZA RNA POLYMERASE PA ENDONUCLEASE
-
There are provided inter alia metalloenzyme inhibitors, such as inhibitors of influenza A RNA dependent RNA polymerase PA subunit endonuclease, and methods of synthesis and use of the same.
- -
-
Paragraph 0465
(2017/09/27)
-
- Synthesis and biological evaluation of deferiprone-resveratrol hybrids as antioxidants, Aβ1–42aggregation inhibitors and metal-chelating agents for Alzheimer's disease
-
A series of deferiprone-resveratrol hybrids have been designed and synthesized as multitarget-directed ligands (MTDLs) through merging the chelating moiety 3-hydroxypyridin-4-one into the structure of resveratrol, a natural antioxidant agent and β-amyloid peptide (Aβ) aggregation inhibitor. The in?vitro biological evaluation revealed that most of these newly synthesized compounds exhibited good inhibitory activity against self-induced Aβ1–42aggregation, excellent antioxidant activity and potent metal chelating capability. Compounds 3i and 4f were identified as the most promising MTDLs with triple functions, possessing micromolar IC50values for Aβ1–42aggregation inhibition, greater 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS?+) scavenging activity than Trolox and similar pFe(III) values to that of deferiprone.
- Xu, Ping,Zhang, Minkui,Sheng, Rong,Ma, Yongmin
-
supporting information
p. 174 - 186
(2017/01/05)
-
- Synthesis of some novel 1,2,3-triazole derivatives containing kojic acid moiety and evaluation for their antioxidant activity
-
Abstract: A series of novel 1,2,3-triazole derivatives containing kojic acid moiety were synthesized by 1,3-dipolar cycloaddition reaction of 2-(azidomethyl)-5-hydroxy-4H-pyran-4-one and 2-(azidomethyl)-5-benzyloxy-4H-pyran-4-one with different alkynes in
- Saraei, Mahnaz,Ghasemi, Zarrin,Dehghan, Gholamreza,Hormati, Marhamat,Ojaghi, Khadijeh
-
p. 917 - 923
(2017/04/14)
-
- Fragment-Based Identification of Influenza Endonuclease Inhibitors
-
The influenza virus is responsible for millions of cases of severe illness annually. Yearly variance in the effectiveness of vaccination, coupled with emerging drug resistance, necessitates the development of new drugs to treat influenza infections. One a
- Credille, Cy V.,Chen, Yao,Cohen, Seth M.
-
supporting information
p. 6444 - 6454
(2016/07/26)
-
- Synthesis of new kojic acid based unnatural α-amino acid derivatives
-
An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond.
- Balakrishna,Payili, Nagaraju,Yennam, Satyanarayana,Uma Devi,Behera, Manoranjan
-
p. 4753 - 4756
(2015/10/28)
-
- INHIBITORS OF CATECHOL O-METHYL TRANSFERASE AND THEIR USE IN THE TREATMENT OF PSYCHOTIC DISORDERS
-
The present invention relates to 4-pyridinone compounds which are inhibitors of catechol O-methyltransferase (COMT), and are useful in the treatment and prevention of neurological and psychiatric disorders and diseases in which COMT enzyme is involved. The present invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which COMT is involved
- -
-
Page/Page column 137
(2011/10/03)
-
- Basic 3-hydroxypyridin-4-ones: Potential antimalarial agents
-
3-Hydroxypyridin-4-ones selectively bind iron under biological conditions and one such compound has found application in the treatment of thalassaemia-linked iron overload. Related molecules have also been demonstrated to possess an antimalarial effect at levels which are non-toxic to mammalian cells. In an attempt to improve the efficiency of such molecules we have investigated the effect of introducing basic nitrogen centres into 3-hydroxypyridin-4-ones in an attempt to achieve targeting to lysosomes and other intracellular acidic vacuoles. Several of the compounds reported in this communication possess enhanced antimalarial activity over that of the simple hydroxypyridinone class.
- Dehkordi, Lotfollah S.,Liu, Zu D.,Hider, Robert C.
-
p. 1035 - 1047
(2008/09/20)
-
- Synthesis and cytotoxicity evaluation of metal-chelator-bearing flavone, carbazole, dibenzofuran, xanthone, and anthraquinone
-
2-(Aryloxymethyl)-5-benzyloxy-1-methyl-1H-pyridin-4-ones 8a-8g, 2-(aryloxymethyl)-5-hydroxy-4H-pyran-4-ones 9a-9g, and 2-(aryloxymethyl)-5-hydroxy-1-methyl-1H-pyridin-4-ones 10a-10g were prepared from the known 5-benzyloxy-2-(hydroxymethyl)pyran-4-one (3) in a good overall yield. These compounds were evaluated in vitro against a three-cell lines panel consisting of MCF7 (breast), NCI-H460 (lung), and SF-268 (CNS), and the active compounds passed on for evaluation in the full panel of 60 human tumor cell lines derived from nine cancer cell types. The results indicated that 5-hydroxy derivatives are more favorable than their corresponding 5-benzyloxy precursors (10a-10g vs. 8a-8g), and 1-methyl-1H-pyridin-4-ones are more favorable than their corresponding pyran-4(1H)-ones (10a-10g vs. 9a-9g). Among these three types of compounds, 2-(aryloxymethyl)-5-hydroxy-1-methyl-1H-pyridin-4-ones 10a-10g were the most cytotoxic; they inhibited the growth of almost all the cancer cells tested. On the contrary, compound 8a (a mean GI50 = 27.8 μM), 8b (38.5), 8d (11.0), and 8e (30.5) are especially active against the growth of SK-MEL-5 (a melanoma cancer cell) with a GI50 of 0.01, 5.65, 0.55, and 0.03 μM, respectively (cf. Table 2).
- Chen, Yeh-Long,Chen, Po-Hsu,Chung, Chao-Ho,Li, Kuang-Chieh,Jeng, Haw-Yaun,Tzeng, Cherng-Chyi
-
p. 778 - 786
(2007/10/03)
-
- Design of novel hybrid vitamin C derivatives: Thermal stability and biological activity
-
Novel hybrid L-ascorbic acid (vitamin C) derivatives with other biologically active substances, 5-hydroxy-2-hydroxymethyl-β-pyrone (kojic acid) and α-tocopherol (vitamin E), linked at the C-2 or C-3 hydroxyl group were synthesized, and their thermal stability and inhibitory effects on tyrosinase activity, active oxygen species (AOS), and free radicals were estimated in vitro. It was found that a hydrophilic derivative, 2-O-(5- hydroxy-4H-pyran-4-one-2-methyl)-L-ascorbic acid (1), exhibited good thermal stability and inhibitory activities against tyrosinase-catalyzed melanin formation, AOS, and free radicals compared to vitamin C and its conventional derivatives (such as the 2-phosphate, 6-stearate and 2,6-dipalmitate, and 2- O-octadecylascorbic acid), as well as vitamin E, kojic acid, and arbutin. It is apparent that 1 has the biological properties of vitamin C and kojic acid, and acts synergistically. The hydroxyl groups at the C-3 position of the vitamin C moiety and the C-5 position of the kojic acid moiety are critical for the biological activities. We consider that the kojic acid moiety of 1 counterbalances the diminution of the biological activity due to shielding of the biologically important C-2 hydroxyl group of the vitamin C moiety. In addition, the thermal stability was significantly improved relative to not only vitamin C but also kojic acid. Further, a lipophilic derivative, 3-O- [(α-tocopheryloxy)-2-hydroxypropyl]-D-ascorbic acid, 2, was far more stable than vitamin C and its typical lipophilic derivatives. Compound 2 exhibited almost the same inhibitory activities against tyrosinase-catalyzed melanin formation, AOS, and free radicals as typical lipophilic derivatives, although these biological activities of 2 were lower than those of vitamin C.
- Morisaki, Kazuo,Ozaki, Shoichiro
-
p. 1647 - 1655
(2007/10/03)
-