Synthesis and biological studies of 4′, 7, 8-trihydroxy-isoflavone metal complexes

Tang, Lijun; Chen, Xiang; Sun, Yuna; Jia, Yali; Lu, Jing; Han, Ying; Jiang, Xing; Cheng, Chan-Chan; He, Cheng-Cheng; Qiu, Peihong; Li, Xiaokun

doi:10.1016/j.jinorgbio.2011.08.019

Cited by 14 publications

(2 citation statements)

References 41 publications

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“…Expression and purification of human 5-lipooxygenase 5-LOX was expressed as a non-tagged protein and used as a crude ammonium sulfate protein fraction (17,18), while 15-LOX-2 was expressed and purified as a histagged protein, as published previously (19).…”

Section: Preparation Of Isoflavones (General Procedure)mentioning

confidence: 99%

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

et al. 2014

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Continuing our search to find more potent and selective 5-LOX inhibitors, we present now the enzymatic evaluation of seventeen isoflavones (IR) and nine isoflavans (HIR), and their in vitro and in cellulo potency against human leukocyte 5-LOX. Of the 26 compounds tested, 10 isoflavones and 9 isoflavans possessed micromolar potency, but only three were selective against 5-LOX (IR-2, HIR-303 and HIR-309), with IC 50 values at least 10 times lower than those of 12-LOX, 15-LOX-1 and 15-LOX-2. Of these three, IR-2 (6,7-dihydroxy-4-methoxy-isoflavone, known as texasin) was the most selective 5-LOX inhibitor, with over 80-fold potency difference, SMD studies supported these findings. The presence of the catechol group on ring A (6,7-dihydroxy versus 7,8-dihydroxy) correlated with their biological activity, but the reduction of ring C, converting the isoflavones to isoflavans, and the substituent positions on ring B did not affect their potency against 5-LOX. Computer docking of the three most selective inhibitors to the crystal structure of human leukocyte 5-LOX confirmed these SAR experimental results. Two of the most potent/selective inhibitors (HIR-303 and HIR-309) were reductive inhibitors and were potent against 5-LOX in human whole blood, indicating that isoflavans can be potent and selective inhibitors against human leukocyte 5-LOX in vitro and in cellulo.

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Section: Preparation Of Isoflavones (General Procedure)mentioning

confidence: 99%

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

et al. 2014

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“…Chromone based compounds have been incorporated in cancer-targeted therapeutic drug molecules which were capable of inhibiting different types of cancer targets, viz., TNF αsignaling and protein kinases [16]. Copper (II) chromone complexes have shown cytotoxicity against different phenotypes of cancer cell lines with varied potencies [17][18][19]. The cytotoxic activity of Cu(II) chromone Schiff base complexes on cell proliferation of chemoresistant lung cancer (A549) and breast (MCF-7) cancer cell line was evaluated and the complexes were capable of effectively overcoming cisplatin resistance in these cell lines which was attributed to chelation of the chromone ligand with metal ion [20].…”

Section: Introductionmentioning

confidence: 99%

Copper (II)-based halogen-substituted chromone antitumor drug entities: Studying biomolecular interactions with ct-DNA mediated by sigma hole formation and cytotoxicity activity

Arjmand¹,

Khursheed²,

Roisnel³

et al. 2020

Bioorganic Chemistry

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Copper-based antitumor drug entities 1-3 derived from substituted (F -, Br -, -CH 3 ) 3formylchromone pharmacophore were synthesized and thoroughly characterized by spectroscopic and single X-ray crystallographic studies. These complexes show structural novelty due to presence of the X-bonds in chromone scaffold which could facilitate higher propensity for nucleic acids via sigma σ-hole interactions. Therefore, structure-activity relationship of 1-3 was studied by performing ct-DNA binding, pBR322 cleavage and cytotoxicity activity to validate their potential to act as chemotherapeutic drug entities. The binding studies of 1-3 with ct-DNA were carried out employing many biophysical techniques and the corroborative results of these experiments showed intercalation mode of binding and the order of binding was found to be 2 > 1 >3. The structure of drug entities could facilitated strong halogen bonding interaction(in case of 1 &2) and stability of X bond was rationalized by sigma hole region of positive electrostatic potential on the surface of C-X covalent bond, as determined by gas phase B3LYP computational DFT studies. Interestingly, 2 exhibited most avid binding affinity due to presence of Brelectron withdrawing and polarizable group. Further, cleavage studies of 1-3 with pBR322 plasmid DNA were performed which demonstrated significant cleavage activity , the supercoiled form (Form I) of plasmid DNA was converted to nicked form (Form II) with the appearance of linearized form(Form III) in between two, implicating lethal double strand breaks of DNA. 2 showed predominantly higher cleavage activity following the similar trend as observed for binding studies.The cytotoxicity of the complexes 1-3 was evaluated by MTT assay against the human liver carcinoma (Huh-7) and prostate cancer (DU-145) cell lines; complex 2 exhibited specific and selective cytotoxicity for the DU-145 cancer cell line with LC 50 value of 1.6μM. Highlights Substituted chromone Copper (II) complexes were synthesized and characterized.  DFT computational studies were also performed.  Electrophoretic studies revealed an oxidative cleavage pathway.  Cytotoxicity was evaluated against the human liver carcinoma (Huh-7) and prostate cancer (DU-145) cell lines.  Copper (II) complex 2 exhibited selective cytotoxicity against DU-145 cell line at GI 50 =1.6μM.

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Production of 3-O-xylosyl quercetin in Escherichia coli

Pandey

Malla

Simkhada

et al. 2012

Appl Microbiol Biotechnol

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Quercetin, a flavonol aglycone, is one of the most abundant flavonoids with high medicinal value. The bioavailability and pharmacokinetic properties of quercetin are influenced by the type of sugars attached to the molecule. To efficiently diversify the therapeutic uses of quercetin, Escherichia coli was harnessed as a production factory by the installation of various plant and bacterial UDP-xylose sugar biosynthetic genes. The genes encoding for the UDP-xylose pathway enzymes phosphoglucomutase (nfa44530), glucose-1-phosphate uridylyltransferase (galU), UDP-glucose dehydrogenase (calS8), and UDP-glucuronic acid decarboxylase (calS9) were overexpressed in E. coli BL21 (DE3) along with a glycosyltransferase (arGt-3) from Arabidopsis thaliana. Furthermore, E. coli BL21(DE3)/∆pgi, E. coli BL21(DE3)/∆zwf, E. coli BL21(DE3)/∆pgi∆zwf, and E. coli BL21(DE3)/∆pgi∆zwf∆ushA mutants carrying the aforementioned UDP-xylose sugar biosynthetic genes and glycosyltransferase and the galU-integrated E. coli BL21(DE3)/∆pgi host harboring only calS8, calS9, and arGt-3 were constructed to enhance whole-cell bioconversion of exogeneously supplied quercetin into 3-O-xylosyl quercetin. Here, we report the highest production of 3-O-xylosyl quercetin with E. coli BL21 (DE3)/∆pgi∆zwf∆ushA carrying UDP-xylose sugar biosynthetic genes and glycosyltransferase. The maximum concentration of 3-O-xylosyl quercetin achieved was 23.78 mg/L (54.75 μM), representing 54.75 % bioconversion, which was an ~4.8-fold higher bioconversion than that shown by E. coli BL21 (DE3) with the same set of genes when the reaction was carried out in 5-mL culture tubes with 100 μM quercetin under optimized conditions. Bioconversion was further improved by 98 % when the reaction was scaled up in a 3-L fermentor at 36 h.

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Synthesis and biological studies of 4′, 7, 8-trihydroxy-isoflavone metal complexes

Cited by 14 publications

References 41 publications

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

Enzymatic Studies of Isoflavonoids as Selective and Potent Inhibitors of Human Leukocyte 5‐Lipo‐Oxygenase

Copper (II)-based halogen-substituted chromone antitumor drug entities: Studying biomolecular interactions with ct-DNA mediated by sigma hole formation and cytotoxicity activity

Production of 3-O-xylosyl quercetin in Escherichia coli

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