Design, synthesis and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers.

Abstract:

:Deregulation of many kinases is directly linked to cancer development and the tyrosine kinase family is one of the most important targets in current cancer therapy regimens. In this study, we have designed and synthesized a series of thieno[2,3-d]pyrimidine derivatives as an EGFR and HER2 tyrosine kinase inhibitors. All the synthesized compounds were evaluated in vitro for their inhibitory activities against EGFRWT; and the most active compounds that showed promising IC50 values against EGFRWT were tested in vitro for their inhibitory activities against mutant EGFRT790M and HER2 kinases. Moreover, the antitumor activities of these compounds were tested against four cancer cell lines (HepG2, HCT-116, MCF-7 and A431). Compounds 13g, 13h and 13k exhibited the highest activities against the examined cell lines with IC50 values ranging from 7.592 ± 0.32 to 16.006 ± 0.58 µM comparable to that of erlotinib (IC50 ranging from 4.99 ± 0.09 to 13.914 ± 0.36 µM). Furthermore, the most potent antitumor agent (13k) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in MCF-7 cell line. The results indicated that this compound arrests G2/M phase of the cell cycle and it is a good apoptotic agent. Finally, molecular docking studies showed a good binding pattern of the synthesized compounds with the prospective target, EGFRWT and EGFRT790M.

journal_name

Bioorg Chem

journal_title

Bioorganic chemistry

authors

Elmetwally SA,Saied KF,Eissa IH,Elkaeed EB

doi

10.1016/j.bioorg.2019.102944

subject

Has Abstract

pub_date

2019-07-01 00:00:00

pages

102944

eissn

0045-2068

issn

1090-2120

pii

S0045-2068(18)31098-8

journal_volume

88

pub_type

杂志文章
  • Novel Linezolid analogues with antiparasitic activity against Hymenolepis nana.

    abstract::The stereoselective synthesis and anti- Hymenolepis nana activity of six Linezolid-type compounds, obtained by chemical modification of l-Alanine, are reported in this work. The synthetic strategy was to prepare diasteromeric N,N-dibenzylamino oxazolidinones 1 and 2, and coupling with 4-(4-bromophenyl)morpholine (3) t...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104359

    authors: Alcántar-Zavala E,Hernández-Guevara E,Ochoa-Terán A,Montes-Ávila J,Estrada-Zavala EA,Salazar-Medina AJ,Alday E,Cabrera A,Aguirre G,Miranda-Soto V,Velazquez C,Díaz-Camacho SP,Medina-Franco JL

    更新日期:2020-12-01 00:00:00

  • An alkali tolerant α-l-rhamnosidase from Fusarium moniliforme MTCC-2088 used in de-rhamnosylation of natural glycosides.

    abstract::Analkali tolerant α-l-rhamnosidase has been purified to homogeneity from the culture filtrate of a new fungal strain, Fusarium moniliforme MTCC-2088, using concentration by ultrafiltration and cation exchange chromatography on CM cellulose column. The molecular mass of the purified enzyme has been found to be 36.0 kDa...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.11.027

    authors: Kumar D,Yadav S,Yadava S,Yadav KDS

    更新日期:2019-03-01 00:00:00

  • Spectroscopic investigation of the interaction of water-soluble azocalix[4]arenes with bovine serum albumin.

    abstract::In this work, three hydrosoluble azocalix[4]arene derivatives, 5-(o-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]arene (o-MAC-Calix), 5-(m-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]arene (m-MAC-Calix) and 5-(p-methylphenylazo)-25,26,27-tris(carboxymethoxy)-28-hydroxycalix[4]a...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2014.12.002

    authors: Fan P,Wan L,Shang Y,Wang J,Liu Y,Sun X,Chen C

    更新日期:2015-02-01 00:00:00

  • Withanolides from Physalis peruviana showing nitric oxide inhibitory effects and affinities with iNOS.

    abstract::A phytochemical study to obtain new nitric oxide (NO) inhibitors resulted in the isolation of five new withanolides from the whole plants of Physalis peruviana. The structures were determined on the basis of extensive NMR spectroscopic data analysis as well as the time-dependent density functional theory (TDDFT) elect...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.03.051

    authors: Dong B,An L,Yang X,Zhang X,Zhang J,Tuerhong M,Jin DQ,Ohizumi Y,Lee D,Xu J,Guo Y

    更新日期:2019-06-01 00:00:00

  • Apoptosis: A target for anticancer therapy with novel cyanopyridines.

    abstract::One of the many methods of treating cancer is to terminate the uncontrolled growth of cancer cells. So, aiming the apoptotic pathway is an exciting approach to finding new anticancer agents. A novel series of cyanopyridines was designed and synthesized for antiproliferative evaluation. 2-Amino-6-(4-(benzyloxy)phenyl)-...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.103481

    authors: Ismail MMF,Farrag AM,Harras MF,Ibrahim MH,Mehany ABM

    更新日期:2020-01-01 00:00:00

  • Scaffold hopping and redesign approaches for quinazoline based urea derivatives as potent VEGFR-2 inhibitors.

    abstract::In our attempt to discover effective anticancer agents, three series of novel quinazoline-based compounds have been designed, synthesized and tested as VEGFR-2 inhibitors. Five quinazoline -2-carboxamide derivatives (5d, 5e, 5 h, 5i, 5j) revealed potent nanomolar VEGFR-2 inhibition with IC50 values of 12.1, 40.3, 15.5...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.103961

    authors: Hadi SRAE,Lasheen DS,Soliman DH,Elrazaz EZ,Abouzid KAM

    更新日期:2020-08-01 00:00:00

  • Bis-coumarins; non-cytotoxic selective urease inhibitors and antiglycation agents.

    abstract::The current study is concerned with the identification of lead molecules based on the bis-coumarin scaffold having selective urease inhibitory and antiglycation activities. For that purpose, bis-coumarins (1-44) were synthesized and structurally characterized by different spectroscopic techniques. Eight derivatives 4,...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.103170

    authors: Salar U,Nizamani A,Arshad F,Khan KM,Fakhri MI,Perveen S,Ahmed N,Choudhary MI

    更新日期:2019-10-01 00:00:00

  • Pyran-2-one derivatives from Croton crassifolius as potent apoptosis inducers in HepG2 cells via p53-mediated Ras/Raf/ERK pathway.

    abstract::Chemical investigation of the roots of Croton crassifolius led to the isolation of five pyran-2-one derivatives, including two brand new compounds (1-2), one new natural product (3) and two known compounds (4-5). Their structures and absolute configurations were established by spectroscopic analyses as well as compari...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.05.020

    authors: Tian JL,Yao GD,Zhang YY,Lin B,Zhang Y,Li LZ,Huang XX,Song SJ

    更新日期:2018-09-01 00:00:00

  • 8-Chrysoeriol, as a potential BCL-2 inhibitor triggers apoptosis of SW1990 pancreatic cancer cells.

    abstract::8-Chrysoeriol, a bioactive flavanoid, was firstly identified to bind directly to BCL-2 as BH3 mimetics by structure-based virtual ligand screening. And 3D docking model revealed the molecular basis of 8-Chrysoeriol targeting to BCL-2. The interaction between 8-Chrysoeriol and BCL-2 was further confirmed using Microsca...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.01.042

    authors: Zhang Y,Li Z,Min Q,Palida A,Zhang Y,Tang R,Chen L,Li H

    更新日期:2018-04-01 00:00:00

  • Novel HLA-A2 restricted antigenic peptide derivatives with high affinity for the treatment of breast cancer expressing NY-ESO-1.

    abstract::Tumor immunotherapy based on specific tumor antigen has become the focus for breast cancer, and research into cancer/testes antigens (CTA) is progressing. As an important member in the CTA, NY-ESO-1 plays a crucial role in the treatment and prognosis of breast cancer. In this study, we aimed to improve the binding abi...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104138

    authors: Shi W,Tong Z,Qiu Q,Yue N,Guo W,Zou F,Zhou D,Li J,Huang W,Qian H

    更新日期:2020-10-01 00:00:00

  • 1,2,3-Triazole-based kojic acid analogs as potent tyrosinase inhibitors: Design, synthesis and biological evaluation.

    abstract::A series of kojic acid-derived compounds 6a-p bearing aryloxymethyl-1H-1,2,3-triazol-1-yl moiety were designed by modifying primary alcoholic group of kojic acid as tyrosinase inhibitors. The target compounds 6a-p were synthesized via click reaction. All compounds showed very potent anti-tyrosinase activity (IC50s = 0...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.10.069

    authors: Ashooriha M,Khoshneviszadeh M,Khoshneviszadeh M,Moradi SE,Rafiei A,Kardan M,Emami S

    更新日期:2019-02-01 00:00:00

  • Design, synthesis, biological evaluation and molecular modeling of novel 1H-pyrrolo[2,3-b]pyridine derivatives as potential anti-tumor agents.

    abstract::A class of 3-substituted 1H-pyrrolo[2,3-b]pyridine derivatives were designed, synthesized and evaluated for their in vitro biological activities against maternal embryonic leucine zipper kinase (MELK). Among these derivatives, the optimized compound 16h exhibited potent enzyme inhibition (IC50 = 32 nM) and excellent a...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.103474

    authors: Wang R,Chen Y,Yang B,Yu S,Zhao X,Zhang C,Hao C,Zhao D,Cheng M

    更新日期:2020-01-01 00:00:00

  • Identification of human, rat and mouse hydrolyzing enzymes bioconverting amino acid ester prodrug of ketoprofen.

    abstract::Alkyl ester prodrugs are well known to be bioconverted by carboxylesterases, particularly in rodents' by first-pass metabolism in the systemic circulation and liver. However, the bioconversion of structurally more complex esters with polar functional groups is less well understood, especially in humans. Therefore, it ...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.09.018

    authors: Huttunen KM

    更新日期:2018-12-01 00:00:00

  • Design, synthesis, biological evaluation and molecular docking of new 1,3,4-oxadiazole homonucleosides and their double-headed analogs as antitumor agents.

    abstract::A novel series of homonucleosides and their double-headed analogs containing theophylline, 1,3,4-oxadiazole, and variant nucleobases was designed and synthesized. The new derivatives were fully characterized by HRMS, FT-IR, 1H NMR, and 13C NMR. The cytotoxic activities of all prepared compounds were screened in vitro ...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104558

    authors: El Mansouri AE,Oubella A,Mehdi A,AitItto MY,Zahouily M,Morjani H,Lazrek HB

    更新日期:2020-12-15 00:00:00

  • Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria.

    abstract::Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104136

    authors: Zhan G,Miao R,Zhang F,Chang G,Zhang L,Zhang X,Zhang H,Guo Z

    更新日期:2020-09-01 00:00:00

  • Synthesis and biological evaluation of benzofuran-based 3,4,5-trimethoxybenzamide derivatives as novel tubulin polymerization inhibitors.

    abstract::A new series of derivatives characterized by the presence of the 3,4,5-trimethoxylbenzamide substituted benzofurans were synthesized and evaluated for antiproliferative activity against four cancer cell lines and one normal human cell line. Among them, derivative 6g with greatest cytotoxicity significantly inhibited t...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104076

    authors: Li Q,Jian XE,Chen ZR,Chen L,Huo XS,Li ZH,You WW,Rao JJ,Zhao PL

    更新日期:2020-09-01 00:00:00

  • Design, synthesis and anti leukemia cells proliferation activities of pyrimidylaminoquinoline derivatives as DOT1L inhibitors.

    abstract::A series of novel pyrimidylaminoquinoline derivatives 8(a-i) and 9(a-i) containing amino side chain, and the bisaminoquinoline analogs 3(b-e) have been designed and synthesized by structural modifications on a lead DOT1L inhibitor, 3a. All the compounds have been evaluated for their DOT1L inhibitory activities. The re...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.07.022

    authors: Zhang L,Chen Y,Liu N,Li L,Xiao S,Li X,Chen K,Luo C,Chen S,Chen H

    更新日期:2018-10-01 00:00:00

  • Ellagitannin and flavonoid constituents from Agrimonia pilosa Ledeb. with their protein tyrosine phosphatase and acetylcholinesterase inhibitory activities.

    abstract::A new ellagitannin, agritannin (1), a new flavone glycoside, agriflavone (2), and another flavone glycoside with spectroscopic data reported for the first time, kaempferol-3-O-[(S)-3-hydroxy-3-methylglutaryl (1→6)]-β-d-glucoside (3), along with 16 known compounds were isolated from the aerial parts of Agrimonia pilosa...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2017.04.017

    authors: Nguyen DH,Seo UM,Zhao BT,Le DD,Seong SH,Choi JS,Min BS,Woo MH

    更新日期:2017-06-01 00:00:00

  • Mitochondria-targeted triphenylphosphonium conjugated glycyrrhetinic acid derivatives as potent anticancer drugs.

    abstract::Glycyrrhetinic acid has been usually studied for their anti-tumor activities. However, the low bioavailability and poor aqueous solubility as well as limited intracellular accumulation have limited their utility. In this present study, a series of new glycyrrhetinic acid conjugates with a triphenylphosphonium cation (...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.12.036

    authors: Jin L,Dai L,Ji M,Wang H

    更新日期:2019-04-01 00:00:00

  • Correlation study on methoxylation pattern of flavonoids and their heme-targeted antiplasmodial activity.

    abstract::A library of 33 polymethoxylated flavones (PMF) was evaluated for heme-binding affinity by biomimetic MS assay and in vitro antiplasmodial activity on two strains of P. falciparum. Stability of heme adducts was discussed using the dissociation voltage at 50% (DV50). No correlation was observed between the methoxylatio...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.104243

    authors: Ortiz S,Vásquez-Ocmín PG,Cojean S,Bouzidi C,Michel S,Figadère B,Grougnet R,Boutefnouchet S,Maciuk A

    更新日期:2020-11-01 00:00:00

  • Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.

    abstract::In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacet...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2020.103721

    authors: Xu A,He F,Zhang X,Li X,Ran Y,Wei C,James Chou C,Zhang R,Wu J

    更新日期:2020-05-01 00:00:00

  • Synthesis and evaluation of novel benzotropolones as Atg4B inhibiting autophagy blockers.

    abstract::Autophagy is an intracellular degradation/recycling pathway that provides nutrients and building blocks to cellular metabolism and keeps the cytoplasm clear of obsolete proteins and organelles. During recent years, dysregulated autophagy activity has been reported to be a characteristic of many different disease types...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.03.021

    authors: Tanc M,Cleenewerck M,Kurdi A,Roelandt R,Declercq W,De Meyer G,Augustyns K,Martinet W,Van der Veken P

    更新日期:2019-06-01 00:00:00

  • Cytotoxicity of oleanolic and ursolic acid derivatives toward hepatocellular carcinoma and evaluation of NF-κB involvement.

    abstract::Oleanolic and ursolic acids are two ubiquitous isomeric triterpene phytochemicals known for their anticancer activity. A set of derivatives of the two compounds with a modified oxidation state and lipophylicity at C-3 and C-28 positions, were prepared and tested as anticancer agents versus the lines HepG2, Hep3B and H...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.103054

    authors: Fontana G,Bruno M,Notarbartolo M,Labbozzetta M,Poma P,Spinella A,Rosselli S

    更新日期:2019-09-01 00:00:00

  • Mechanistic investigations on substituted benzene sulphonamides as apoptosis inducing anticancer agents.

    abstract::In an approach to develop potent cytotoxic compounds with targeted action, a systematic methodology was employed to design and initially synthesize parent compounds A1, A8, A13 and A14 followed by synthesis of further analogs of A1 (A2-A7) and A8 (A9-A12) with characterization by IR, NMR, mass and elemental techniques...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2019.103539

    authors: Mettu A,Talla V,Thumma S,Naikal James Prameela S

    更新日期:2020-01-01 00:00:00

  • Stereospecificity, substrate, and inhibitory properties of nucleoside diphosphate analogs for creatine and pyruvate kinases.

    abstract::Antiviral alpha-P-borano substituted NTPs are promising chain terminators targeting HIV reverse transcriptase (RT). Activation of antiviral nucleoside diphosphates (NDPs) to NTPs may be carried out by pyruvate kinase (PK) and creatine kinase (CK). Herein, are presented the effects of nucleobase, ribose, and alpha-phos...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2008.03.001

    authors: Wennefors CK,Dobrikov MI,Xu Z,Li P,Shaw BR

    更新日期:2008-08-01 00:00:00

  • Recent advances in synthesis and medicinal chemistry of benzodiazepines.

    abstract::Benzodiazepines (BZDs) represent a diverse class of bicyclic heterocyclic molecules. In the last few years, benzodiazepines have emerged as potential therapeutic agents. As a result, several mild, efficient and high yielding protocols have been developed that offer access to various functionalized benzodiazepines (BZD...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bioorg.2020.103668

    authors: Arora N,Dhiman P,Kumar S,Singh G,Monga V

    更新日期:2020-04-01 00:00:00

  • Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008-2019).

    abstract::Cyclooxygenase-2 is a very important physiological enzyme playing key roles in various biological functions especially in the mechanism of pain and inflammation, among other roles, making it a molecule of high interest to the pharmaceutical community as a target. COX 2 enzyme is induced only during inflammatory proces...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章,评审

    doi:10.1016/j.bioorg.2019.103007

    authors: Sharma V,Bhatia P,Alam O,Javed Naim M,Nawaz F,Ahmad Sheikh A,Jha M

    更新日期:2019-08-01 00:00:00

  • Binding of the natural substrates and products to KDO8P synthase: 31P and 13C solution NMR characterization.

    abstract::Proton decoupled 31P and 13C solution NMR experiments were applied to mixtures of 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDO8P) synthase, with each of its natural substrates, phosphoenolpyruvate and arabinose-5-phosphate (ASP), and product KDO8P to identify the formation of the enzyme-substrate and enzyme-product...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/s0045-2068(03)00064-6

    authors: Kaustov L,Baasov T,Schmidt A

    更新日期:2003-08-01 00:00:00

  • Synthesis and in-vitro anti-leishmanial activity of (4-arylpiperazin-1-yl)(1-(thiophen-2-yl)-9H-pyrido[3,4-b]indol-3-yl)methanone derivatives.

    abstract::In the present study, we have reported synthesis and biological evaluation of a series of fifteen 1-(thiophen-2-yl)-9H-pyrido[3,4-b]indole derivatives against both promastigotes and amastigotes of Leishmania parasites responsible for visceral (L. donovani) and cutaneous (L. amazonensis) leishmaniasis. Among these repo...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2016.11.013

    authors: Ashok P,Chander S,Chow LM,Wong IL,Singh RP,Jha PN,Sankaranarayanan M

    更新日期:2017-02-01 00:00:00

  • Synthesis, molecular docking and xanthine oxidase inhibitory activity of 5-aryl-1H-tetrazoles.

    abstract::5-Aryl-1H-tetrazoles (1-24) were synthesized and screened for their xanthine oxidase (XO) inhibitory activity using allopurinol as standard inhibitor (IC50 = 2.0 ± 0.01 µM). Six compounds 3, 4, 5, 9, 21, and 24 exhibited significant to weak activities with IC50 values in the range of 7.4-174.2 µM. Active compounds wer...

    journal_title:Bioorganic chemistry

    pub_type: 杂志文章

    doi:10.1016/j.bioorg.2018.04.021

    authors: Fatima I,Zafar H,Khan KM,Saad SM,Javaid S,Perveen S,Choudhary MI

    更新日期:2018-09-01 00:00:00