Novel curcumin analogs to overcome EGFR-TKI lung adenocarcinoma drug resistance and reduce EGFR-TKI-induced GI adverse effects.


:Curcumin (1) down-regulates the expression as well as phosphorylation of epidermal growth factor receptor (EGFR) in lung adenocarcinoma cells expressing gefitinib-resistant EGFR. Thirty-seven newly synthesized curcumin analogues including dimethoxycurcumin (2, DMC) were evaluated for their effects on EGFR expression as well as phosphorylation in two gefitinib-resistant lung adenocarcinoma cell lines, CL1-5 (EGFR(wt)) and H1975 (EGFR(L858R+T790M)). Based on the identified structure-activity relationships, methoxy substitution at C-3', C-4', or both positions favored inhibitory activity (compounds 1, 2, 5, 8-15, 17, 36), while compounds with more polar substituents were generally less active in both cell lines. Compound 36 with a fluorine substituent at C-6' and its protonated counterpart 2 did not lose activity, suggesting halogen tolerance. In addition, a conjugated linker was essential for activity. Among all evaluated curcumin derivatives, compound 2 showed the best inhibitory effects on both wild-type and mutant EGFR by efficiently inducing gefitinib-insensitive EGFR degradation. Compound 23 also reduced gefitinib-induced gastrointestinal damage in the non-transformed intestinal epithelial cell line IEC-18.


Bioorg Med Chem


Wada K,Lee JY,Hung HY,Shi Q,Lin L,Zhao Y,Goto M,Yang PC,Kuo SC,Chen HW,Lee KH




Has Abstract


2015-04-01 00:00:00














  • Effect of structurally constrained oxime-ether linker on PPAR subtype selectivity: Discovery of a novel and potent series of PPAR-pan agonists.

    abstract::A novel series of thaizole and oxazole containing phenoxy acetic acid derivatives is reported as PPAR-pan agonists. Incorporation of structurally constrained oxime-ether based linker in the chemotype of a potent PPARδ selective agonist GW-501516 was adapted as designing strategy. In vitro, selected test compounds 12a,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Makadia P,Shah SR,Pingali H,Zaware P,Patel D,Pola S,Thube B,Priyadarshini P,Suthar D,Shah M,Giri S,Trivedi C,Jain M,Patel P,Bahekar R

    更新日期:2011-01-15 00:00:00

  • Dimeric cinnamoylamide analogues for regulation of tyrosinase activity in melanoma cells: A role of diamide-link chain length.

    abstract::Dimeric cynnamoyl analogues (DCAs) with depigmenting activity have been developed. In this study, a role of diamide linkage chain length of DCAs as a tyrosinase inhibitor was investigated on tyrosinase inhibitory activity, antioxidative activity, hydrophobicity and anti-melanogenesis as well as structural characterist...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Ha JH,Park SN

    更新日期:2018-12-15 00:00:00

  • Synthesis and biological evaluation of 4,5-dihydro-1H-pyrazole derivatives as potential nNOS/iNOS selective inhibitors. Part 2: Influence of diverse substituents in both the phenyl moiety and the acyl group.

    abstract::In a preliminary article, we reported a series of 4,5-dihydro-1H-pyrazole derivatives as neuronal nitric oxide synthase (nNOS) inhibitors. Here we present the data about the inhibition of inducible nitric oxide synthase (iNOS) of these compounds. In general, we can confirm that these pyrazoles are nNOS selective inhib...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Carrión MD,Chayah M,Entrena A,López A,Gallo MA,Acuña-Castroviejo D,Camacho ME

    更新日期:2013-07-15 00:00:00

  • 1,2,4-Triazole and 1,3,4-oxadiazole analogues: Synthesis, MO studies, in silico molecular docking studies, antimalarial as DHFR inhibitor and antimicrobial activities.

    abstract::1,2,4-Triazole and 1,3,4-oxadiazole analogues are of interest due to their potential activity against microbial and malarial infections. In search of suitable antimicrobial and antimalarial compounds, we report here the synthesis, characterization and biological activities of 1,2,4-triazole and 1,3,4-oxadiazole analog...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Thakkar SS,Thakor P,Doshi H,Ray A

    更新日期:2017-08-01 00:00:00

  • A continuous flow synthesis and derivatization of 1,2,4-thiadiazoles.

    abstract::A continuous flow process is presented that enables the efficient synthesis and derivatization of 1,2,4-thiadiazole heterocycles. Special attention was given to the safe handling of the versatile yet hazardous trichloromethane sulfenylchloride reagent including its in-line quenching in order to eliminate malodourous a...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Baumann M,Baxendale IR

    更新日期:2017-12-01 00:00:00

  • Discovery of a new type of scaffold for the creation of novel tyrosinase inhibitors.

    abstract::Tyrosinase is known as the key enzyme for melanin biosynthesis, which is effective in preventing skin injury by ultra violet (UV). In past decades, tyrosinase has been well studied in the field of cosmetics, medicine, agriculture and environmental sciences, and a lot of tyrosinase inhibitors have been developed for th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Oyama T,Takahashi S,Yoshimori A,Yamamoto T,Sato A,Kamiya T,Abe H,Abe T,Tanuma SI

    更新日期:2016-09-15 00:00:00

  • Thiophene bioisosteres of GluN2B selective NMDA receptor antagonists: Synthesis and pharmacological evaluation of [7]annuleno[b]thiophen-6-amines.

    abstract::Thiophene bioisosteres of potent GluN2B receptor negative allosteric modulators were prepared and evaluated pharmacologically. The five-step synthesis of 4,5,7,8-tetrahydro[7]annuleno[b]thiophen-6-one (10) was considerably improved by carboxylation of thiophene-3-carboxylic acid (8) in the first reaction step. Reducti...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Baumeister S,Schepmann D,Wünsch B

    更新日期:2020-01-15 00:00:00

  • Optimization of thiazole analogues of resveratrol for induction of NAD(P)H:quinone reductase 1 (QR1).

    abstract::NAD(P)H:quinone reductase 1 (QR1) belongs to a class of enzymes called cytoprotective enzymes. It exhibits its cancer protective activity mainly by inhibiting the formation of intracellular semiquinone radicals, and by generating α-tocopherolhydroquinone, which acts as a free radical scavenger. It is therefore believe...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mayhoub AS,Marler L,Kondratyuk TP,Park EJ,Pezzuto JM,Cushman M

    更新日期:2012-12-15 00:00:00

  • A CoMSIA study on the adenosine kinase inhibition of pyrrolo[2,3-d]pyrimidine nucleoside analogues.

    abstract::The structural requirements of pyrrolo[2,3-d]pyrimidine nucleoside (PPN) analogues as adenosine kinase (AK) inhibitors were in silico studied by using CoMSIA method. All models were trained with 32 compounds, after which they were evaluated for predictive ability with additional 5 compounds. Quantitative information o...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Caballero J,Fernández M,González-Nilo FD

    更新日期:2008-05-01 00:00:00

  • Preclinical evaluation of a CXCR4-specific (68)Ga-labelled TN14003 derivative for cancer PET imaging.

    abstract::Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. In our pursuit of a CXCR4-specific radiotracer, we designed and syn...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: George GP,Stevens E,Åberg O,Nguyen QD,Pisaneschi F,Spivey AC,Aboagye EO

    更新日期:2014-01-15 00:00:00

  • Study on dual-site inhibitors of acetylcholinesterase: Highly potent derivatives of bis- and bifunctional huperzine B.

    abstract::Natural (-)-huperzine B (HupB), isolated from Chinese medicinal herb, displayed moderate inhibitory activity of acetylcholinesterase (AChE). Based on the active dual-site of AChE, a series of novel derivatives of bis- and bifunctional HupB were designed and synthesized. The AChE inhibition potency of most derivatives ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: He XC,Feng S,Wang ZF,Shi Y,Zheng S,Xia Y,Jiang H,Tang XC,Bai D

    更新日期:2007-02-01 00:00:00

  • A class of sulfonamide carbonic anhydrase inhibitors with neuropathic pain modulating effects.

    abstract::A series of benzene sulfonamide carbonic anhydrase (CA, EC inhibitors which incorporate lipophilic 4-alkoxy- and 4-aryloxy moieties, together with several derivatives of ethoxzolamide and sulfanilamide are reported. These derivatives were investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA,...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Carta F,Di Cesare Mannelli L,Pinard M,Ghelardini C,Scozzafava A,McKenna R,Supuran CT

    更新日期:2015-04-15 00:00:00

  • Modification at the C9 position of the marine natural product isoaaptamine and the impact on HIV-1, mycobacterial, and tumor cell activity.

    abstract::As part of an investigation to generate optimized drug leads from marine natural pharmacophores for the treatment of neoplastic and infectious diseases, a series of novel isoaaptamine analogs were prepared by coupling acyl halides to the C9 position of isoaaptamine (2) isolated from the Aaptos sponge. This library of ...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Gul W,Hammond NL,Yousaf M,Bowling JJ,Schinazi RF,Wirtz SS,de Castro Andrews G,Cuevas C,Hamann MT

    更新日期:2006-12-15 00:00:00

  • Design, Synthesis and Anticancer Evaluation of New Substituted Thiophene-Quinoline Derivatives.

    abstract::A series of new isoxazolyl, triazolyl and phenyl based 3-thiophen-2-yl-quinoline derivatives were synthesized adopting click chemistry approach. In addition, the synthesis of new useful synthon, (2-chloroquinolin-3-yl) (thiophen-2-yl) methanol, is reported. The obtained compounds were characterized by spectral data an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Othman DIA,Selim KB,El-Sayed MA,Tantawy AS,Amen Y,Shimizu K,Okauchi T,Kitamura M

    更新日期:2019-10-01 00:00:00

  • Synthesis and binding affinity of novel mono- and bivalent morphinan ligands for κ, μ, and δ opioid receptors.

    abstract::A novel series of homo- and heterodimeric ligands containing κ/μ agonist and μ agonist/antagonist pharmacophores joined by a 10-carbon ester linker chain were synthesized and evaluated for their in vitro binding affinity at κ, μ, and δ opioid receptors, and their functional activities were determined at κ and μ recept...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhang B,Zhang T,Sromek AW,Scrimale T,Bidlack JM,Neumeyer JL

    更新日期:2011-05-01 00:00:00

  • Relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors.

    abstract::1,3,5,6-tetrahydroxyxanthone was synthesized. The relationship between protective effect of xanthone on endothelial cells and endogenous nitric oxide synthase inhibitors was investigated. Endothelial cells were treated with ox-LDL (100 microg/mL) for 48 h. Adhesion of monocytes to endothelial cells and release of lact...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Jiang DJ,Hu GY,Jiang JL,Xiang HL,Deng HW,Li YJ

    更新日期:2003-11-17 00:00:00

  • Synthesis of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives as inhibitors of human liver glycogen phosphorylase a.

    abstract::A series of 5-chloro-N-aryl-1H-indole-2-carboxamide derivatives were prepared and evaluated as inhibitors of human liver glycogen phosphorylase a (hLGPa). One compound, 5-chloro-N-[4-(1,2-dihydroxyethyl)phenyl]-1H-indole-2-carboxamide (2f), inhibited hLGPa with an IC(50) of 0.90microM. The pyridine analogue of 2f show...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Onda K,Suzuki T,Shiraki R,Yonetoku Y,Negoro K,Momose K,Katayama N,Orita M,Yamaguchi T,Ohta M,Tsukamoto S

    更新日期:2008-05-15 00:00:00

  • Design, synthesis, and evaluation of alpha-ketoheterocycles as class C beta-lactamase inhibitors.

    abstract::A series of specific alpha-ketoheterocycles (benzoxazole, thiazole, imidazole, tetrazole, and thiazole-4-carboxylate) has been synthesized in order to assess their potential as beta-lactamase inhibitors. The syntheses were achieved either by construction of the heterocycle (benzoxazole) from an appropriate alpha-hydro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kumar S,Pearson AL,Pratt RF

    更新日期:2001-08-01 00:00:00

  • Phenyl substituted 3-hydroxypyridin-2(1H)-ones: inhibitors of influenza A endonuclease.

    abstract::Inhibition of the endonuclease activity of influenza RNA-dependent RNA polymerase is recognized as an attractive target for the development of new agents for the treatment of influenza infection. Our earlier study employing small molecule fragment screening using a high-resolution crystal form of pandemic 2009 H1N1 in...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Parhi AK,Xiang A,Bauman JD,Patel D,Vijayan RS,Das K,Arnold E,Lavoie EJ

    更新日期:2013-11-01 00:00:00

  • Concise syntheses of arabinogalactans with beta-(1-->6)-linked galactopyranose backbones and alpha-(1-->3)- and alpha-(1-->2)-linked arabinofuranose side chains.

    abstract::4-methoxyphenyl glycosides of 2,3''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl tetraose (16), 3',2''''-bis-alpha-L-arabinofuranosyl branched beta-D-(1-->6)-linked galactopyranosyl hexaose (27), and a twentyose (42) consisting of beta-(1-->6)-linked D-galactopyranosyl pentadecaoligosac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Li A,Kong F

    更新日期:2005-02-01 00:00:00

  • Selection and characterization of human antibodies neutralizing Bacillus anthracis toxin.

    abstract::A less than adequate therapeutic plan for the treatment of anthrax in the 2001 bioterrorism attacks has highlighted the importance of developing alternative or complementary therapeutic approaches for biothreat agents. In these regards passive immunization possesses several important advantages over active vaccination...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Zhou B,Carney C,Janda KD

    更新日期:2008-02-15 00:00:00

  • Differential receptor binding characteristics of consecutive phenylalanines in micro-opioid specific peptide ligand endomorphin-2.

    abstract::Endogenous opioid peptides consist of a conserved amino acid residue of Phe(3) and Phe(4), although their binding modes for opioid receptors have not been elucidated in detail. Endomorphin-2, which is highly selective and specific for the mu opioid receptor, possesses two Phe residues at the consecutive positions 3 an...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Honda T,Shirasu N,Isozaki K,Kawano M,Shigehiro D,Chuman Y,Fujita T,Nose T,Shimohigashi Y

    更新日期:2007-06-01 00:00:00

  • Design, synthesis and primary activity evaluation of L-arginine derivatives as amino-peptidase N/CD13 inhibitors.

    abstract::A series of L-arginine derivatives were designed, synthesized and assayed for their activities against amino-peptidase N (APN)/CD13 and metalloproteinase-2 (MMP-2). The results showed that most compounds exhibited high inhibitory activities against APN and low activities against MMP-2. Within this series, two compound...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Mou J,Fang H,Jing F,Wang Q,Liu Y,Zhu H,Shang L,Wang X,Xu W

    更新日期:2009-07-01 00:00:00

  • Inactivation of the human papillomavirus-16 E6 oncoprotein by organic disulfides.

    abstract::We are investigating compounds that could be useful in the treatment of neoplastic lesions of the cervix by acting on the oncoprotein E6 of human papillomavirus-16. The E6 protein contains two potential zinc-binding domains that are required for most of its functions. We have published tests that measure (i) the relea...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Beerheide W,Sim MM,Tan YJ,Bernard HU,Ting AE

    更新日期:2000-11-01 00:00:00

  • Anthranilic diamides derivatives as potential ryanodine receptor modulators: Synthesis, biological evaluation and structure activity relationship.

    abstract::A series of novel anthranilic diamides derivatives (7a-s) containing halogen, trifluoromethyl group and cyano group were designed, synthesized, and characterized by melting point, 1H NMR, 13C NMR and elemental analyses. The bioactivity revealed that most of them showed moderate to excellent activities against oriental...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Liu JB,Li FY,Dong JY,Li YX,Zhang XL,Wang YH,Xiong LX,Li ZM

    更新日期:2018-07-23 00:00:00

  • Glycosyl bis-porphyrin conjugates: synthesis and potential application in PDT.

    abstract::Syntheses of new glycosylated neutral and cationic porphyrin dimers linked at the meso-position via a flexible hydrocarbon chain are described. A detailed 1H and 13C NMR study allows their complete structural elucidation. The UV-visible, fluorescence and MALDI mass spectra are also presented. Photocytotoxicities of th...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Sol V,Chaleix V,Champavier Y,Granet R,Huang YM,Krausz P

    更新日期:2006-12-01 00:00:00

  • Novel trans-2-aryl-cyclopropylamine analogues as potent and selective dipeptidyl peptidase IV inhibitors.

    abstract::A series of trans-2-aryl-cyclopropylamine derived compounds were synthesized and evaluated their biological activities against DPP-IV. The structure-activity relationships (SAR) led to the discovery of novel series of DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely relate...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Tsai TY,Hsu T,Chen CT,Cheng JH,Yeh TK,Chen X,Huang CY,Chang CN,Yeh KC,Hsieh SH,Chien CH,Chang YW,Huang CH,Huang YW,Huang CL,Wu SH,Wang MH,Lu CT,Chao YS,Jiaang WT

    更新日期:2009-03-15 00:00:00

  • The chemical synthesis and antibiotic activity of a diverse library of 2-aminobenzimidazole small molecules against MRSA and multidrug-resistant A. baumannii.

    abstract::Multidrug-resistant bacterial infections continue to be a rising global health concern. Herein is described the development of a class of novel 2-aminobenzimidazoles with antibiotic activity. These active 2-aminobenzimidazoles retain their antibiotic activity against several strains of multidrug-resistant Staphylococc...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Huigens RW 3rd,Reyes S,Reed CS,Bunders C,Rogers SA,Steinhauer AT,Melander C

    更新日期:2010-01-15 00:00:00

  • Syntheses and pharmacological characterization of novel thiazole derivatives as potential mGluR5 PET ligands.

    abstract::Four novel thiazole containing ABP688 derivatives were synthesized and evaluated for their binding affinity towards the metabotropic glutamate receptor subtype 5 (mGluR5). (E)-3-((2-(Fluoromethyl)thiazol-4-yl)ethynyl)cyclohex-2-enone O-methyl oxime (FTECMO), the ligand with the highest binding affinity (K(i)=5.5+/-1.1...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Baumann CA,Mu L,Wertli N,Krämer SD,Honer M,Schubiger PA,Ametamey SM

    更新日期:2010-08-15 00:00:00

  • Enhanced RNA binding of dimerized aminoglycosides.

    abstract::Aminoglycoside antibiotics have recently emerged as an intriguing family of RNA binding molecules and they became leading structures for the design of novel RNA ligands. The demystification of the aminoglycoside-RNA recognition phenomenon is required for the development of superior binders. To explore the existence of...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Michael K,Wang H,Tor Y

    更新日期:1999-07-01 00:00:00