Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site.

Abstract:

:The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an appropriately positioned acceptor for Cys241β in the otherwise hydrophobic subpocket A.

journal_name

Medchemcomm

journal_title

MedChemComm

authors

Da C,Telang N,Hall K,Kluball E,Barelli P,Finzel K,Jia X,Gupton JT,Mooberry SL,Kellogg GE

doi

10.1039/C2MD20320K

subject

Has Abstract

pub_date

2013-01-01 00:00:00

pages

417-421

issue

2

eissn

2040-2503

issn

2040-2511

journal_volume

4

pub_type

杂志文章
  • Exploring the effectiveness of novel benzimidazoles as CB2 ligands: synthesis, biological evaluation, molecular docking studies and ADMET prediction.

    abstract::Herein we continued our previous work on the development of CB2 ligands, reporting the design and synthesis of a series of benzimidazole-containing derivatives that were explored as selective CB2 ligands with binding affinity towards both CB1 and CB2 receptors. Seven out of eighteen compounds exhibited preferential bi...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00461g

    authors: Tonelli M,Cichero E,Mahmoud AM,Rabbito A,Tasso B,Fossa P,Ligresti A

    更新日期:2018-10-10 00:00:00

  • Benzisoxazole: a privileged scaffold for medicinal chemistry.

    abstract::The benzisoxazole analogs represent one of the privileged structures in medicinal chemistry and there has been an increasing number of studies on benzisoxazole-containing compounds. The unique benzisoxazole scaffold also exhibits an impressive potential as antimicrobial, anticancer, anti-inflammatory, anti-glycation a...

    journal_title:MedChemComm

    pub_type: 杂志文章,评审

    doi:10.1039/c7md00449d

    authors: Rakesh KP,Shantharam CS,Sridhara MB,Manukumar HM,Qin HL

    更新日期:2017-10-31 00:00:00

  • Development of a peptide-based bifunctional chelator conjugated to a cytotoxic drug for the treatment of melanotic melanoma.

    abstract::The cytotoxic drug gemcitabine (GEM) has been conjugated to receptor-binding peptides to target melanoma tumors. A hexapeptide having a Lys-Gly-His-Lys sequence (pep-1), an octapeptide with an Arg-Gly-Asp-Lys-Gly-His-Lys sequence (pep-2), a GEM-conjugated Lys-Gly-His-Lys peptide (GEM-pep-3) and a GEM-conjugated Asp-Gl...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00638a

    authors: Gaonkar RH,Baishya R,Paul B,Dewanjee S,Ganguly S,Debnath MC,Ganguly S

    更新日期:2018-03-06 00:00:00

  • Synthesis, conformational preferences, and biological activity of conformational analogues of the microtubule-stabilizing agents, (-)-zampanolide and (-)-dactylolide.

    abstract::Zampanolide and dactylolide are microtubule-stabilizing polyketides possessing potent cytotoxicity towards a variety of cancer cell lines. Using our understanding of the conformational preferences of the macrolide core in both natural products, we hypothesized that analogues lacking the C17-methyl group would maintain...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c9md00164f

    authors: Henry JL,Wilson MR,Mulligan MP,Quinn TR,Sackett DL,Taylor RE

    更新日期:2019-04-09 00:00:00

  • Synthesis of dihydronaphthalene analogues inspired by combretastatin A-4 and their biological evaluation as anticancer agents.

    abstract::The natural products colchicine and combretastatin A-4 (CA4) have provided inspiration for the discovery and development of a wide array of derivatives and analogues that inhibit tubulin polymerization through a binding interaction at the colchicine site on β-tubulin. A water-soluble phosphate prodrug salt of CA4 (ref...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00322j

    authors: Maguire CJ,Chen Z,Mocharla VP,Sriram M,Strecker TE,Hamel E,Zhou H,Lopez R,Wang Y,Mason RP,Chaplin DJ,Trawick ML,Pinney KG

    更新日期:2018-08-24 00:00:00

  • Rational design and optimization of selenophenes with basic side chains as novel potent selective estrogen receptor modulators (SERMs) for breast cancer therapy.

    abstract::To increase the diversity of estrogen receptor (ER) ligands having novel structures and activities, series of selenophene derivatives with a basic side chain (BSC) were synthesized and their biological activity as subtype-selective antagonists for the ER was explored. Compared with the selenophenes without a BSC, most...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00163k

    authors: Luo J,Hu Z,Xiao Y,Yang T,Dong C,Huang J,Zhou HB

    更新日期:2017-05-24 00:00:00

  • Discovery of 4,6-disubstituted pyrimidines as potent inhibitors of the heat shock factor 1 (HSF1) stress pathway and CDK9.

    abstract::Heat shock factor 1 (HSF1) is a transcription factor that plays key roles in cancer, including providing a mechanism for cell survival under proteotoxic stress. Therefore, inhibition of the HSF1-stress pathway represents an exciting new opportunity in cancer treatment. We employed an unbiased phenotypic screen to disc...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c6md00159a

    authors: Rye CS,Chessum NE,Lamont S,Pike KG,Faulder P,Demeritt J,Kemmitt P,Tucker J,Zani L,Cheeseman MD,Isaac R,Goodwin L,Boros J,Raynaud F,Hayes A,Henley AT,de Billy E,Lynch CJ,Sharp SY,Te Poele R,Fee LO,Foote KM,Gree

    更新日期:2016-08-01 00:00:00

  • Structure activity relationship of 2-arylalkynyl-adenine derivatives as human A3 adenosine receptor antagonists.

    abstract::Recognition of nucleosides at adenosine receptors (ARs) is supported by multiple X-ray structures, but the structure of an adenine complex is unknown. We examined the selectivity of predicted A1AR and A3AR adenine antagonists that incorporated known agonist affinity-enhancing N6 and C2 substituents. Adenines with A1AR...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00317c

    authors: Yu J,Mannes P,Jung YH,Ciancetta A,Bitant A,Lieberman DI,Khaznadar S,Auchampach JA,Gao ZG,Jacobson KA

    更新日期:2018-10-18 00:00:00

  • Structure-Based Design, Synthesis by Click Chemistry and in Vivo Activity of Highly Selective A3 Adenosine Receptor Agonists.

    abstract::2-Arylethynyl derivatives of (N)-methanocarba adenosine 5'-uronamides are selective A3AR (adenosine receptor) agonists. Here we substitute a 1,2,3-triazol-1-yl linker in place of the rigid, linear ethynyl group to eliminate its potential metabolic liability. Docking of nucleosides containing possible short linker moie...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/C4MD00571F

    authors: Tosh DK,Paoletta S,Chen Z,Crane S,Lloyd J,Gao ZG,Gizewski ET,Auchampach JA,Salvemini D,Jacobson KA

    更新日期:2015-01-01 00:00:00

  • Exploiting the co-reliance of tumours upon transport of amino acids and lactate: Gln and Tyr conjugates of MCT1 inhibitors.

    abstract::Glutamine and tyrosine-based amino acid conjugates of monocarboxylate transporter types 1 and 2 inhibitors (MCT1/2) were designed, synthesized and evaluated for their potency in blocking the proliferation of a human B lymphoma cell line that expresses the transporters Asct2, LAT1 and MCT1. Appropriate placement of an ...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/C5MD00579E

    authors: Nair RN,Mishra JK,Li F,Tortosa M,Yang C,Doherty JR,Cameron M,Cleveland JL,Roush WR,Bannister TD

    更新日期:2016-05-01 00:00:00

  • Synthesis, structure-activity relationship and binding mode analysis of 4-thiazolidinone derivatives as novel inhibitors of human dihydroorotate dehydrogenase.

    abstract::A series of 4-thiazolidinone derivatives were synthesized and evaluated as novel human dihydroorotate dehydrogenase (hDHODH) inhibitors. Compounds 26 and 31 displayed IC50 values of 1.75 and 1.12 μM, respectively. The structure-activity relationship was summarized. Further binding mode analysis revealed that compound ...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00081b

    authors: Zeng F,Qi T,Li C,Li T,Li H,Li S,Zhu L,Xu X

    更新日期:2017-04-26 00:00:00

  • Neuropilin-1 peptide-like ligands with proline mimetics, tested using the improved chemiluminescence affinity detection method.

    abstract::Many reports have suggested that NRP-1 acts as a co-receptor for VEGF-A165 and boosts tumour growth and metastasis. This NRP-1, due to its important role in tumour progression, triggered interest in the design of new molecules able to significantly inhibit NRP-1/VEGF-A165 interaction to suppress pathological angiogene...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00537k

    authors: Puszko AK,Sosnowski P,Tymecka D,Raynaud F,Hermine O,Lepelletier Y,Misicka A

    更新日期:2019-01-25 00:00:00

  • High affinity rigidified AT2 receptor ligands with indane scaffolds.

    abstract::Rigidification of the isobutyl side chain of drug-like AT2 receptor agonists and antagonists that are structurally related to the first reported selective AT2 receptor agonist 1 (C21) delivered bioactive indane derivatives. Four enantiomer pairs were synthesized and the enantiomers were isolated in an optical purity >...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c9md00402e

    authors: Wallinder C,Sköld C,Sundholm S,Guimond MO,Yahiaoui S,Lindeberg G,Gallo-Payet N,Hallberg M,Alterman M

    更新日期:2019-11-18 00:00:00

  • A complex game of hide and seek: the search for new antifungals.

    abstract::Fungal infections directly affect millions of people each year. In addition to the invasive fungal infections of humans, the plants and animals that comprise our primary food source are also susceptible to diseases caused by these eukaryotic microbes. The need for antifungals, not only for our medical needs, but also ...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/C6MD00222F

    authors: Ngo HX,Garneau-Tsodikova S,Green KD

    更新日期:2016-07-01 00:00:00

  • Identification and biological evaluation of novel benzothiazole derivatives bearing a pyridine-semicarbazone moiety as apoptosis inducers via activation of procaspase-3 to caspase-3.

    abstract::Three series of compounds were designed, synthesized and evaluated for their in vitro anticancer activity against a procaspase-3 over-expression cancer cell line (U937) and a procaspase-3 no-expression cancer cell line (MCF-7) to rule out off-target effects. Biological evaluation led to the identification of a series ...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00624e

    authors: Ma J,Ni X,Gao Y,Huang K,Liu J,Wang Y,Chen R,Wang C

    更新日期:2019-02-25 00:00:00

  • Synthesis and in vitro evaluation of substituted 3-cinnamoyl-4-hydroxy-pyran-2-one (CHP) in pursuit of new potential antituberculosis agents.

    abstract::Tuberculosis is an ever-evolving infectious disease that urgently needs new drugs. In the search for new antituberculosis agents, a library of 3-cinnamoyl-4-hydroxy-6-methyl-2H-pyran-2-ones (CHPs) (2a-2y) was synthesized and evaluated against a standard virulent laboratory strain of Mycobacterium tuberculosis H37Rv. O...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00366h

    authors: Bhat ZS,Ul Lah H,Rather MA,Maqbool M,Ara T,Ahmad Z,Yousuf SK

    更新日期:2017-12-06 00:00:00

  • Discovery and biological evaluation of N5-substituted 6,7-dioxo-6,7-dihydropteridine derivatives as potent Bruton's tyrosine kinase inhibitors.

    abstract::Bruton's tyrosine kinase (BTK) plays a critical role in B cell receptor (BCR)-mediated signaling pathways responsible for the development and function of B cells, which makes it an attractive target for the treatment of many types of B-cell malignancies. Herein, a series of N5-substituted 6,7-dioxo-6,7-dihydropteridin...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00019k

    authors: Chen H,Song P,Diao Y,Hao Y,Dou D,Wang W,Fang X,Wang Y,Zhao Z,Ding J,Li H,Xie H,Xu Y

    更新日期:2018-03-13 00:00:00

  • Correction: Recent updates in the discovery and development of novel antimalarial drug candidates.

    abstract::[This corrects the article DOI: 10.1039/C7MD00637C.]. ...

    journal_title:MedChemComm

    pub_type: 杂志文章,已发布勘误

    doi:10.1039/c8md90009d

    authors: Okombo J,Chibale K

    更新日期:2018-03-02 00:00:00

  • Synthesis and in vitro study of novel borneol derivatives as potent inhibitors of the influenza A virus.

    abstract::Herein, we present the design and synthesis of a series of novel heterocyclic derivatives of (-)-borneol and (-)-isoborneol as potent inhibitors of the influenza A virus. All compounds were tested for their toxicity against MDCK cells and for virus-inhibiting activity against the influenza virus A/Puerto Rico/8/34 (H1...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c6md00657d

    authors: Sokolova AS,Yarovaya OI,Semenova MD,Shtro AA,Orshanskaya IR,Zarubaev VV,Salakhutdinov NF

    更新日期:2017-03-03 00:00:00

  • Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer's disease.

    abstract::A series of indole derivatives was designed and synthesised to improve on activity and circumvent pharmacokinetic limitations experienced with the structurally related compound, ladostigil. The compounds consisted of a propargylamine moiety (a known MAO inhibitor and neuroprotector) at the N1 position and a ChE inhibi...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00569e

    authors: Denya I,Malan SF,Enogieru AB,Omoruyi SI,Ekpo OE,Kapp E,Zindo FT,Joubert J

    更新日期:2018-01-16 00:00:00

  • Kaolin alleviates the toxicity of graphene oxide for mammalian cells.

    abstract::The development of novel nanoscale vehicles for drug delivery promotes the growth of interest in investigations of interaction between nanomaterials. In this paper, we report the in vitro studies of eukaryotic cell physiological response to incubation with graphene oxide and planar kaolin nanoclay. Graphene family mat...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00633d

    authors: Rozhina E,Batasheva S,Danilushkina A,Kryuchkova M,Gomzikova M,Cherednichenko Y,Nigamatzyanova L,Akhatova F,Fakhrullin R

    更新日期:2019-06-10 00:00:00

  • Recent progress in the development of metal complexes as β-amyloid imaging probes in the brain.

    abstract::In this review, we have focused on the recent progress in metal complexes that are able to bind to β-amyloid (Aβ) species. We have discussed various radioactive complexes of 99mTc, 68Ga, 64Cu, 89Zr, and 111In, which were designed as Aβ imaging agents for positron emission tomography (PET) and single photon emission co...

    journal_title:MedChemComm

    pub_type: 杂志文章,评审

    doi:10.1039/c7md00064b

    authors: Chen K,Cui M

    更新日期:2017-05-16 00:00:00

  • Discovery of a tetrazolyl β-carboline with in vitro and in vivo osteoprotective activity under estrogen-deficient conditions.

    abstract::β-Carbolines have been assessed for osteoclastogenesis. However, their effect on osteoblasts during estrogen deficiency is still unclear. Here, a series of novel piperazine and tetrazole tag β-carbolines have been synthesized and examined for osteoblast differentiation in vitro. In vitro data suggest that compound 8g ...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c8md00109j

    authors: Karvande A,Khan S,Khan I,Singh D,Khedgikar V,Kushwaha P,Ahmad N,Kothari P,Dhasmana A,Kant R,Trivedi R,Chauhan PMS

    更新日期:2018-06-12 00:00:00

  • Synthesis and synergistic antifungal effects of monoketone derivatives of curcumin against fluconazole-resistant Candida spp.

    abstract::Twenty-three monoketone derivatives of curcumin were synthesized to investigate the synergy with fluconazole against fluconazole-resistant Candida spp. The minimal inhibitory concentration (MIC80) and the fractional inhibitory concentration index (FICI) of the antifungal synergist fluconazole were measured against flu...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c6md00649c

    authors: Zhao F,Dong HH,Wang YH,Wang TY,Yan ZH,Yan F,Zhang DZ,Cao YY,Jin YS

    更新日期:2017-03-17 00:00:00

  • Synthesis and biological activity evaluation of novel peroxo-bridged derivatives as potential anti-hepatitis B virus agents.

    abstract::Previous studies have demonstrated that natural steroid compounds containing a peroxide bridge exhibited potential anti-hepatitis B virus activity. To continue our research, a simple and regioselective methodology, using Eosin Y as a clean photosensitized oxidation catalyst, was developed for the synthesis of a peroxi...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c6md00344c

    authors: Jia M,Zhao R,Xu B,Yan W,Chu F,Gu H,Xie T,Xiang H,Ren J,Chen D,Wang P,Lei H

    更新日期:2016-10-19 00:00:00

  • Synthesis of DNA-coupled isoquinolones and pyrrolidines by solid phase ytterbium- and silver-mediated imine chemistry.

    abstract::DNA-encoded libraries of chemically synthesized compounds are an important small molecule screening technology. The synthesis of encoded compounds in solution is currently restricted to a few DNA-compatible and water-tolerant reactions. Encoded compound synthesis of short DNA-barcodes covalently connected to solid sup...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c9md00042a

    authors: Potowski M,Kunig VBK,Losch F,Brunschweiger A

    更新日期:2019-02-26 00:00:00

  • Effect of antimalarial drug primaquine and its derivatives on the ionization potential of hemoglobin: A QM/MM study.

    abstract::We used quantum mechanics/molecular mechanics calculations to test if antimalarial primaquine (PQ) and its derivatives aid the conversion of hemoglobin to methemoglobin by binding to hemoglobin and merely lowering hemoglobin's ionization potential (IP). Our results showed that PQ and its derivatives do not significant...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/C3MD00045A

    authors: Liu H,Ding Y,Walker LA,Doerksen RJ

    更新日期:2013-08-01 00:00:00

  • Recent advances in combretastatin based derivatives and prodrugs as antimitotic agents.

    abstract::The dynamic and crucial role of tubulin in different cellular functions rendered it a promising target in anticancer drug development. Combretastatin A-4 (CA-4), an inhibitor of tubulin polymerization isolated from natural sources, is a lead molecule with significant cytotoxicity against tumour cells. Owing to its non...

    journal_title:MedChemComm

    pub_type: 杂志文章,评审

    doi:10.1039/c7md00227k

    authors: Seddigi ZS,Malik MS,Saraswati AP,Ahmed SA,Babalghith AO,Lamfon HA,Kamal A

    更新日期:2017-07-04 00:00:00

  • Discovery of pyridyl-based inhibitors of Plasmodium falciparum N-myristoyltransferase.

    abstract::N-Myristoyltransferase (NMT) represents an attractive drug target in parasitic infections such as malaria due to its genetic essentiality and amenability to inhibition by drug-like small molecules. Scaffold simplification from previously reported inhibitors containing bicyclic cores identified phenyl derivative 3, pro...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c5md00242g

    authors: Yu Z,Brannigan JA,Rangachari K,Heal WP,Wilkinson AJ,Holder AA,Leatherbarrow RJ,Tate EW

    更新日期:2015-10-08 00:00:00

  • Cu(ii), Ga(iii) and In(iii) complexes of 2-acetylpyridine N(4)-phenylthiosemicarbazone: synthesis, spectral characterization and biological activities.

    abstract::In this paper, synthesis and characterization of metal complexes [Cu2(L)3]ClO4 (1), [Ga(L)2]NO3·2H2O (2) and [In(L)2]NO3·H2O (3) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) was carried out, including elemental analysis, spectral analysis (IR, UV-vis, NMR), and X-ray crystallography. Complex 1 contains one S-b...

    journal_title:MedChemComm

    pub_type: 杂志文章

    doi:10.1039/c7md00415j

    authors: Wang YT,Fang Y,Zhao M,Li MX,Ji YM,Han QX

    更新日期:2017-10-09 00:00:00