Publications by authors named "Mingli Deng"

15 Publications

  • Page 1 of 1

Development of anti-breast cancer PI3K inhibitors based on 7-azaindole derivatives through scaffold hopping: Design, synthesis and in vitro biological evaluation.

Bioorg Chem 2021 Dec 6;117:105405. Epub 2021 Oct 6.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China. Electronic address:

Breast cancer is the cancer with the highest incidence all over the world. Phosphatidylinositol 3-kinase is an important regulator of intracellular signaling pathways, which is frequently mutated and overexpressed in majority of human breast cancers, and the inhibition of PI3K has been considered as a promising approach for the treatment of the cancer. Here, we report our design and synthesis of new 7-azaindole derivatives as PI3K inhibitors through the scaffold hopping strategy. By varying the groups at the 3-position of 7-azaindole, we identified a series of potent PI3K inhibitors, whose antiproliferative activities against two human breast cancer MCF-7 and MDA-MB-231 cell lines were evaluated. Representative derivatives FD2054 and FD2078 showed better activity than BKM120 in antiproliferation, reduced the levels of phospho-AKT and induced cell apoptosis. All these results suggested that FD2054 and FD2078 are potent PI3K inhibitors that could be considered as potential candidates for the development of anticancer agents.
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http://dx.doi.org/10.1016/j.bioorg.2021.105405DOI Listing
December 2021

Discovery of cinnoline derivatives as potent PI3K inhibitors with antiproliferative activity.

Bioorg Med Chem Lett 2021 09 17;48:128271. Epub 2021 Jul 17.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, China. Electronic address:

Cinnoline is a potential pharmacophore which has rarely been reported for uses as PI3K inhibitors. In this study, a series of cinnoline derivatives were developed as PI3K inhibitors and evaluated for enzymatic and cellular activities. Most compounds displayed nanomolar inhibitory activities against PI3Ks, among which 25 displayed high LLE and micromolar inhibitory potency against three human tumor cell lines (IC = 0.264 μM, 2.04 μM, 1.14 μM).
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http://dx.doi.org/10.1016/j.bmcl.2021.128271DOI Listing
September 2021

Bioisosteric replacements of the indole moiety for the development of a potent and selective PI3Kδ inhibitor: Design, synthesis and biological evaluation.

Eur J Med Chem 2021 Nov 21;223:113661. Epub 2021 Jun 21.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, 200433, China. Electronic address:

Based on indole scaffold, a potent and selective phosphoinositide 3-kinase delta (PI3Kδ) inhibitor, namely FD223, was developed by the bioisosteric replacement drug discovery approach and studied for the treatment of acute myeloid leukemia (AML). In vitro studies revealed that FD223 displays high potency (IC = 1 nM) and selectivity (29-51 fold over other PI3K isoforms) against PI3Kδ, and exhibits efficient inhibition of the proliferation of AML cell lines (MOLM-16, HL-60, EOL-1 and KG-1) by suppressing p-AKT Ser473 thus causing G1 phase arrest during the cell cycle. Further given the favorable pharmacokinetic (PK) profiles of FD223, in vivo studies were evaluated using xenograft model in nude mice, confirming its significant antitumor efficacy meanwhile with no observable toxicity. All these results are comparable to the positive group of Idelalisib (CAL-101), indicating that FD223 has potential for further development as a promising PI3Kδ inhibitor for the treatment of leukemia such as AML.
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http://dx.doi.org/10.1016/j.ejmech.2021.113661DOI Listing
November 2021

A robust etb-type metal-organic framework showing polarity-exclusive adsorption of acetone over methanol for their azeotropic mixture.

Chem Commun (Camb) 2019 Jun 3;55(46):6495-6498. Epub 2019 May 3.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, 200438, China.

We report a robust and rigid etb-type metal-organic framework, in which its pore surface is decorated with flexible ethoxyl groups. It shows unprecedentedly selective adsorption of acetone (E value of 0.355, kinetic diameter of 4.6 Å) over methanol (E value of 0.762, kinetic diameter of 3.6 Å) for their azeotropic mixture.
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http://dx.doi.org/10.1039/c9cc02439eDOI Listing
June 2019

Cobalt substitution in a flexible metal-organic framework: modulating a soft paddle-wheel unit for tunable gate-opening adsorption.

Dalton Trans 2019 Jun 25;48(21):7100-7104. Epub 2019 Mar 25.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, 200438, China.

Developing feasible ways to achieve tunable gate-opening pressure (P) while minimizing the side effects on the adsorption capacity and enthalpy is greatly desired for flexible MOFs. In this work, we focused on solving this issue by cobalt substitution. We showed the successful modulation of the energy required for the reversible transformation of a soft paddle-wheel so that the whole framework presented a substitution-dependent P for CO adsorption.
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http://dx.doi.org/10.1039/c9dt00115hDOI Listing
June 2019

Photoelectrochemical properties of MOF-induced surface-modified TiO photoelectrode.

Nanoscale 2018 Nov;10(43):20339-20346

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.

Heteroatom doping and surface modification with oxides are both important strategies to improve the photoelectrochemical (PEC) activities of TiO2 photoelectrodes. However, it is difficult to combine the two strategies into a single synthesis process. Herein, a simple one-pot synthesis method was developed to modify a TiO2 photoelectrode surface by N-doping while simultaneously modifying the surface with In2O3 and NiO. This method involved growing MOF onto a TiO2 surface with N-containing organic ligands and In and Ni salts as metal precursors, followed by heat treatment at 600 °C. The roles of heteroatom doping and oxide modification are proposed as follows. (i) N-Doping extends the absorption edge of the TiO2 to a longer wavelength region and enhances visible light absorption. (ii) N-Doping together with the passivation of TiO2 surface trap states by oxide modification increases the donor density in TiO2. (iii) The generated suitable interfaces on the surface of TiO2 facilitate photogenerated charge separation and transfer. In comparison with the pristine TiO2 photoelectrode, the metal oxide- and heteroatom-modified TiO2 photoelectrode exhibits superior photoelectrochemical performance under both simulated sunlight and visible light illumination. Suitable substrate of the electrode, appropriate size of the as-synthesized MOF precursors, and choice of ligands and metal ions are important factors for this strategy.
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http://dx.doi.org/10.1039/c8nr06471gDOI Listing
November 2018

Integrating Zeolite-Type Chalcogenide with Titanium Dioxide Nanowires for Enhanced Photoelectrochemical Activity.

Langmuir 2017 11 15;33(47):13634-13639. Epub 2017 Nov 15.

Materials Science and Engineering Program, University of California , Riverside, California 92521, United States.

Developing photoanodes with efficient visible-light harvesting and excellent charge separation still remains a key challenge in photoelectrochemical water splitting. Here zeolite-type chalcogenide CPM-121 is integrated with TiO nanowires to form a heterostructured photoanode, in which crystalline CPM-121 particles serve as a visible light absorber and TiO nanowires serve as an electron conductor. Owing to the small band gap of chalcogenides, the hybrid electrode demonstrates obvious absorption in visible-light range. Electrochemical impedance spectroscopy (EIS) shows that electron transport in the hybrid electrode has been significantly facilitated due to the heterojunction formation. A >3-fold increase in photocurrent is observed on the hybrid electrode under visible-light illumination when it is used as a photoanode in a neutral electrolyte without sacrificial agents. This study opens up a new avenue to explore the potential applications of crystalline porous chalcogenide materials for solar-energy conversion in photoelectrochemistry.
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http://dx.doi.org/10.1021/acs.langmuir.7b02403DOI Listing
November 2017

Discovery of a Novel Series of 7-Azaindole Scaffold Derivatives as PI3K Inhibitors with Potent Activity.

ACS Med Chem Lett 2017 Aug 26;8(8):875-880. Epub 2017 Jul 26.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai 200433, China.

The phosphoinositide 3-kinase (PI3K) inhibitors potently inhibit the signaling pathway of PI3K/AKT/mTOR, which provides a promising new approach for the molecularly targeted cancer therapy. In this work, a novel series of 7-azaindole scaffold derivatives was discovered by the fragment-based growing strategy. The structure-activity relationship profiles identified that the 7-azaindole scaffold derivatives exhibit potent activity against PI3K at molecular and cellular levels as well as cell proliferation in a panel of human tumor cells.
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http://dx.doi.org/10.1021/acsmedchemlett.7b00222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5554905PMC
August 2017

Cation-Exchange Approach to Tuning the Flexibility of a Metal-Organic Framework for Gated Adsorption.

Inorg Chem 2017 May 17;56(9):5069-5075. Epub 2017 Apr 17.

Department of Chemistry, University of California , Riverside, California 92521, United States.

Achieving tailorable gated adsorption by tuning the dynamic behavior of a host porous material is of great interest because of its practical application in gas adsorption and separation. Here we devise a unique cation-exchange approach to tune the dynamic behavior of a flexible anionic framework, [Zn(bptc)(datrz)] (denoted as MAC-6, where Hbptc = [1,1'-biphenyl]-3,3',5,5'-tetracarboxylic acid and Hdatrz = 3,5-diamine-1H-1,2,4-triazole), so as to realize the tailorable gated adsorption. The CO adsorption amount at 273 K can be enhanced by exchanging the counterion of protonated dimethylamine (HDMA) with tetraethylammonium (TEA), tetrabutylammonium (TBA), and tetramethylammonium (TMA), where the adsorption behavior is transferred from nongated to gated adsorption. Interestingly, the P for gate-opening adsorption can be further tuned from 442 to 331 mmHg by simply adjusting the ratio of HDMA and TMA. The origin of this unique tunable property, as revealed by X-ray diffraction experiments and structure models, is rooted at the cation-responsive characteristic of this flexible framework.
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http://dx.doi.org/10.1021/acs.inorgchem.7b00133DOI Listing
May 2017

A highly stable indium phosphonocarboxylate framework as a multifunctional sensor for Cu(2+) and methylviologen ions.

Dalton Trans 2015 Feb;44(8):3794-800

Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P.R. China.

An indium phosphonocarboxylate framework, {H3O[In(pbpdc)]·3H2O}n (InPCF-1) (pbpdc = 4'-phosphonobiphenyl-3,5-dicarboxylate), was hydrothermally synthesized. The structure of InPCF-1 features the inorganic chains as rod-shaped second building units. The rod-packing arrangement results in a three-dimensional (3-D) framework with a novel (3,4,5)-connected net. Studies of the gas adsorption, and thermal and chemical stability of InPCF-1 demonstrated its adsorption capacity for CO2, selective separation of CO2 over O2 and N2, high thermal stability, and a remarkable chemical resistance to boiling water, ethyl alcohol, and methylbenzene. Importantly, InPCF-1 shows a selective and sensitive response to Cu(2+) ions. It also serves as a sensor for methylviologen.
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http://dx.doi.org/10.1039/c4dt03502jDOI Listing
February 2015

A porous metal-organic framework constructed from carboxylate-pyrazolate shared heptanuclear zinc clusters: synthesis, gas adsorption, and guest-dependent luminescent properties.

Inorg Chem 2013 Sep 5;52(18):10368-74. Epub 2013 Sep 5.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University , 220 Handan Road, Shanghai 200433, People's Republic of China.

A three-dimensional porous structure of [Zn7O2(bpdc)4(dmpp)2]·6DEF·10H2O (MAC-7, H2bpdc = 4,4'-biphenyldicarboxylic acid, Hdmpp = 3,5-dimethyl-4-(4'-pyridyl)pyrazole), built of 12-bridged carboxylate-pyrazolate shared Zn7O2 clusters, has been synthesized. Because of the presence of 12-bridged carboxylate-pyrazolate shared building block, MAC-7 is a double-linked pcu-type framework and shows reversible phase transformation. Photoluminescent property studies indicate that MAC-7 could sense nitrobenzene over toluene, p-xylene, and mesitylene by luminescent quenching.
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http://dx.doi.org/10.1021/ic401092jDOI Listing
September 2013

Enhancing CO2 adsorption of a Zn-phosphonocarboxylate framework by pore space partitions.

Chem Commun (Camb) 2013 Jan 16;49(1):78-80. Epub 2012 Nov 16.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, 220 Handan Road, Shanghai 200433, P. R. China.

Using structure-directing agents, pore space partitions of a Zn-phosphonocarboxylate framework have been achieved. Selective adsorption of CO(2) over N(2) has been greatly improved from ca. 9 : 1 to 94 : 1.
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http://dx.doi.org/10.1039/c2cc37174jDOI Listing
January 2013

Metal complexes as templates: syntheses, structures, and luminescent properties of two zinc phosphonocarboxylates with ABW-zeolite topology.

Dalton Trans 2012 Apr 8;41(14):4079-83. Epub 2012 Feb 8.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, China.

Two novel zinc phosphonocarboxylates, Zn(3)(pbc)(2)(bpy)(H(2)O)·H(2)O (1) and Zn(2)(pbc)(2)·Zn(bpy)(H(2)O)(4)·2H(2)O (2) (pbc = 4-phosphono-benzoic acid, bpy = 2,2'-bipyridine), were hydrothermally synthesized and structurally characterized. Both of them exhibit zeolitic ABW topology in which double-zigzag inorganic chains are cross-linked by the organic parts. It is notable that the metal complex Zn(bpy)(H(2)O)(x) plays different roles in the two compounds. In 1, the Zn(bpy)(H(2)O) units coordinate with the phosphonate and carboxylate oxygen atoms and participate in the construction of the three-dimensional framework. In 2, the in situ generated [Zn(bpy)(H(2)O)(4)](2+) cation acts as a template, which directs the ABW-type open-framework by strong hydrogen bonds. It is the first example where a metal complex is used as a template in the synthesis of metal phosphonates. The luminescent properties of 1 and 2 are also investigated.
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http://dx.doi.org/10.1039/c2dt12060gDOI Listing
April 2012

Novel iso-reticular Zn(II) metal-organic frameworks constructed by trinuclear-triangular and paddle-wheel units: synthesis, structure and gas adsorption.

Dalton Trans 2012 Apr 23;41(14):4007-11. Epub 2012 Jan 23.

Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Department of Chemistry, Fudan University, Shanghai, China.

Two novel Zn(II) metal-organic frameworks (MOFs) constructed by trinuclear-triangular and paddle-wheel units, namely {[Zn(5)(dmtrz)(3)(IPA)(3)(OH)]·DMF·H(2)O}(n) (MAC-4, Hdmtrz = 3,5-dimethyl-1H-1,2,4-triazole, H(2)IPA = isophthalic acid, DMF = dimethyl formamide) and {[Zn(5)(dmtrz)(3)(OH-IPA)(3)(OH)]·DMF·5H(2)O}(n) (MAC-4-OH, OH-H(2)IPA = 5-hydroxyisophthalic acid), were solvothermally synthesized. Single-crystal analyses reveal that MAC-4-OH is an iso-reticular framework of MAC-4 with channels functionalized by hydroxyl groups. Gas adsorption reveals that MAC-4-OH shows a significant enhancement for CO(2) uptake compared with that of MAC-4 due to the existence of electrostatic attractive interactions, though its surface area is lower than that of MAC-4.
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http://dx.doi.org/10.1039/c2dt12059cDOI Listing
April 2012

Synthesis of isoreticular zinc(II)-phosphonocarboxylate frameworks and their application in the Friedel-Crafts benzylation reaction.

Chemistry 2011 Sep 4;17(37):10323-8. Epub 2011 Aug 4.

Department of Chemistry and Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Fudan University, 220 Handan Road, Shanghai 200433, P. R. China.

Three isoreticular zinc(II)-phosphonocarboxylate frameworks, namely {[Zn(3)(pbdc)(2)]·2H(3)O}(n) (ZnPC-2), {[Zn(3)(pbdc)(2)]·Hpd·H(3)O·4H(2)O}(n) ([email protected]) and {[Co(1.5)Zn(1.5)(pbdc)(2)]·2H(3)O}(n) (CoZnPC-2) (H(4)pbdc=5-phosphonobenzene-1,3-dicarboxylic acid, pd=pyrrolidine), were solvothermally synthesized. ZnPC-2 has a 3D structure based on trinuclear Zn(II) clusters (Zn(3)-SBU) showing 3D interconnected channels. [email protected] contains an isoreticular framework of ZnPC-2 with small channels blocked by Hpd molecules. In CoZnPC-2, Zn(II) ions in ZnPC-2 are partially substituted by Co(II) ions. The Friedel-Crafts benzylation reactions were carried out over these isoreticular porous materials. The catalytic results reveal that ZnPC-2 is an excellent heterogeneous Lewis acid catalyst with a high selectivity (>90%) towards less bulky para-oriented products. The catalytic reaction has been proved to occur inside the pore of ZnPC-2, and the immobilized Zn(3)-SBUs are the active sites.
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http://dx.doi.org/10.1002/chem.201101239DOI Listing
September 2011
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