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

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

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

abstract：:In the present work, coumarin based pyrazolines (7a-g) have been synthesized and investigated for their in vitro and in vivo anti-inflammatory potential. Amongst the synthesized compounds, compounds 7a, 7d and 7f exhibited significant in vitro anti-inflammatory activity as compared to the standard etoricoxib. Keeping ...

journal_title：MedChemComm

authors： Chandel P,Kumar A,Singla N,Kumar A,Singh G,Gill RK

更新日期：2019-01-23 00:00:00

abstract：:A new iron(iii) complex with 5,7-dichloro-2-methyl-8-quinolinol (HClMQ) as ligands, i.e., [Fe(ClMQ)2Cl] (1), was synthesized and evaluated for its anticancer activity. Compared to the HClMQ ligand, complex 1 showed a higher cytotoxicity towards a series of tumor cell lines, including Hep-G2, BEL-7404, NCI-H460, A549, ...

journal_title：MedChemComm

authors： Zou BQ,Qin QP,Bai YX,Cao QQ,Zhang Y,Liu YC,Chen ZF,Liang H

更新日期：2017-02-01 00:00:00

abstract：:A novel and simplified synthetic scaffold based on pladienolide was designed using a consensus pharmacophore hypothesis. An initial target was synthesized and evaluated to examine the role of the 3-hydroxy group and the methyl groups present at positions 10, 16, 20, 22 in 1, on biological activity. We report the first...

journal_title：MedChemComm

authors： Gundluru MK,Pourpak A,Cui X,Morris SW,Webb TR

更新日期：2011-01-01 00:00:00

abstract：:Two diazabicyclo analogues of maraviroc, in which the azabicyclooctane moiety is replaced by diazabicyclooctane or diazabicyclononane, were synthesized and tested, through a viral neutralization assay, on a panel of six pseudoviruses. The diazabicyclooctane derivative maintained a significant infectivity reduction pow...

journal_title：MedChemComm

authors： Legnani L,Colombo D,Venuti A,Pastori C,Lopalco L,Toma L,Mori M,Grazioso G,Villa S

更新日期：2016-12-16 00:00:00

abstract：:Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus Trypanosoma. As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawback...

journal_title：MedChemComm

authors： Berninger M,Schmidt I,Ponte-Sucre A,Holzgrabe U

更新日期：2017-07-31 00:00:00

abstract：:We previously reported that troponoid compounds profoundly inhibit replication of herpes simplex virus (HSV)-1 and HSV-2 in cell culture, including acyclovir-resistant mutants. Synthesis of 26 alpha-hydroxylated tropolones (αHTs) led to a preliminary structure-activity relationship highlighting the potency of bi-pheny...

journal_title：MedChemComm

authors： Berkowitz AJ,Franson AD,Gazquez Cassals A,Donald KA,Yu AJ,Garimallaprabhakaran AK,Morrison LA,Murelli RP

更新日期：2019-05-30 00:00:00

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

authors： Chen K,Cui M

更新日期：2017-05-16 00:00:00

abstract：:Porphyrins are tetrapyrrolic macrocyclic ligands known for their affinity towards neoplastic tissues and once radiolabeled with a suitable diagnostic radioisotope could potentially be used for the imaging of tumorous lesions. In the present study, an unsymmetrically substituted porphyrin derivative namely 5-(p-amino-p...

journal_title：MedChemComm

authors： Guleria M,Das T,Vats K,Amirdhanayagam J,Mathur A,Sarma HD,Dash A

更新日期：2019-02-22 00:00:00

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

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

abstract：:A combinatorial library of 6 × 106 cyclic peptides was synthesized in the one bead-two compound format, with each bead displaying a unique cyclic peptide on its surface and a linear peptide encoding tag in its interior. Screening of the library against K-Ras identified compounds that bound K-Ras with submicromolar aff...

journal_title：MedChemComm

authors： Wu X,Upadhyaya P,Villalona-Calero MA,Briesewitz R,Pei D

更新日期：2013-02-01 00:00:00

abstract：:The type III secretion system injectisome is a syringe-like multimembrane spanning nanomachine that is essential to the pathogenicity but not viability of many clinically relevant Gram-negative bacteria, such as enteropathogenic Escherichia coli, Salmonella enterica and Pseudomonas aeruginosa. Due to the rise in antib...

journal_title：MedChemComm

authors： Lyons BJE,Strynadka NCJ

更新日期：2019-06-20 00:00:00

abstract：:A series of 18 new 5-[3-(4-aryl-1-piperazinyl)propoxy]coumarin derivatives from the corresponding bromoalkyl derivatives have been designed and synthesized by us using a microwave-assisted protocol. Radioligand binding assays of this series of compounds as well as a previously synthesized series of 17 structurally-sim...

journal_title：MedChemComm

authors： Ostrowska K,Grzeszczuk D,Głuch-Lutwin M,Gryboś A,Siwek A,Dobrzycki Ł,Trzaskowski B

更新日期：2017-07-03 00:00:00

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

journal_title：MedChemComm

authors： Okombo J,Chibale K

更新日期：2018-03-02 00:00:00

abstract：:The high storage capacities and excellent biocompatibilities of zinc(ii) metal-organic frameworks (Zn-MOFs) have made them outstanding candidates as drug delivery carriers. Recent studies on the pH-responsive processes based on carrier-drug interactions have proven them to be the most efficient and effective way to co...

journal_title：MedChemComm

authors： Liu W,Pan Y,Xiao W,Xu H,Liu D,Ren F,Peng X,Liu J

更新日期：2019-10-17 00:00:00

abstract：:Urinary tract infections (UTIs) are amongst the most common and prevalent infectious diseases worldwide, with uropathogenic Escherichia coli (UPEC) reported as the main causative pathogen. Fluoroquinolone antibiotics are commonly used to treat UTIs but for infections involving UPEC biofilms, which are commonly associa...

journal_title：MedChemComm

authors： Verderosa AD,Harris J,Dhouib R,Totsika M,Fairfull-Smith KE

更新日期：2019-02-25 00:00:00

abstract：:Transcriptomic phenotypes defined for melanoma have been reported to correlate with sensitivity to various drugs. In this study, we aimed to define a minimal signature that could be used to distinguish melanoma sub-types in vitro, and to determine suitable drugs by which these sub-types can be targeted. By using prima...

journal_title：MedChemComm

authors： Senses KM,Ghasemi M,Akbar MW,Isbilen M,Fallacara AL,Frankenburg S,Schenone S,Lotem M,Botta M,Gure AO

更新日期：2017-01-01 00:00:00

abstract：:In the last three decades, protein and nucleic acid structure determination and comprehension of the mechanisms, leading to their physiological and pathological functions, have become a cornerstone of biomedical sciences. A deep understanding of the principles governing the fates of cells and tissue at the molecular l...

journal_title：MedChemComm

authors： Bernetti M,Cavalli A,Mollica L

更新日期：2017-01-30 00:00:00

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

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

abstract：:A series of novel indazole-pyrone hybrids were synthesized by a one pot reaction between N-alkyl-6(5)-nitroindazoles and 2-pyrone (4-hydroxy-6-methyl-2H-pyran-2-one) using indium or stannous chloride as the reducing system in the presence of acetic acid in tetrahydrofuran. The hybrid molecules were obtained in good to...

journal_title：MedChemComm

authors： El Ghozlani M,Bouissane L,Berkani M,Mojahidi S,Allam A,Menendez C,Cojean S,Loiseau PM,Baltas M,Rakib EM

更新日期：2018-11-19 00:00:00

abstract：:[This corrects the article DOI: 10.1039/C0MD00060D.]. ...

journal_title：MedChemComm

authors： Chen T,Mei WJ,Wong YS,Liu J,Liu Y,Xie HS,Zheng WJ

更新日期：2018-03-19 00:00:00

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

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

abstract：:A novel series of 2-pyrazoline derivatives were designed, synthesized, and evaluated for cholinesterase (ChE) inhibitory, Aβ anti-aggregating and neuroprotective activities. Among these, 3d, 3e, 3g, and 3h were established as the most potent and selective BChE inhibitors (IC50 = 0.5-3.9 μM), while 3f presented dual in...

journal_title：MedChemComm

authors： Unsal-Tan O,Tüylü Küçükkılınç T,Ayazgök B,Balkan A,Ozadali-Sari K

更新日期：2019-05-09 00:00:00

abstract：:Diabetes mellitus is a chronic, complex and multifactorial disease associated characteristically with hyperglycemia. One of the most recently approved antidiabetic drug classes for clinical use are sodium-glucose cotransporter type 2 (SGLT-2) inhibitors. SGLT-2 is a protein expressed in the kidneys, responsible for gl...

journal_title：MedChemComm

authors： da Silva PN,da Conceição RA,do Couto Maia R,de Castro Barbosa ML

更新日期：2018-06-06 00:00:00

abstract：:New derivatives of aminoglycosides containing 6'-carboxylic acid or 6'-amide on their ring I were designed, synthesized and their ability to readthrough nonsense mutations was examined in vitro, along with the protein translation inhibition in prokaryotic and eukaryotic systems. The observed structure-activity relatio...

journal_title：MedChemComm

authors： Sabbavarapu NM,Pieńko T,Zalman BH,Trylska J,Baasov T

更新日期：2018-02-02 00:00:00

abstract：:A series of cyclic peptides were designed and prepared to investigate the physicochemical properties that affect oral bioavailabilty of this chemotype in rats. In particular, the ionization state of the peptide was examined by the incorporation of naturally occurring amino acid residues that are charged in differing r...

journal_title：MedChemComm

authors： Rand AC,Leung SS,Eng H,Rotter CJ,Sharma R,Kalgutkar AS,Zhang Y,Varma MV,Farley KA,Khunte B,Limberakis C,Price DA,Liras S,Mathiowetz AM,Jacobson MP,Lokey RS

更新日期：2012-10-01 00:00:00

abstract：:Classical aminoglycoside antibiotics are obsolete or hampered by the emergence of drug resistant bacteria. Recent discoveries of antifungal amphiphilic kanamycins offer new strategies for reviving and repurposing these old drugs. A simple structural modification turns the clinically obsolete antibacterial kanamycin in...

journal_title：MedChemComm

authors： Subedi YP,AlFindee MN,Takemoto JY,Chang CT

更新日期：2018-04-17 00:00:00

abstract：:A focused library of 24 N-aryl urea derivatives was prepared and evaluated against serine esterases of Mycobacterium tuberculosis (Mtb) Rv3802c and Mtb Ag85C. The members of the library were evaluated for both selectivity and mode of inhibition. Furan-based urea derivative 6c was found to be the most potent non-covale...

journal_title：MedChemComm

authors： Vartak A,Goins C,de Moura VCN,Schreidah CM,Landgraf AD,Lin B,Du J,Jackson M,Ronning DR,Sucheck SJ

更新日期：2019-06-04 00:00:00

abstract：:The dopamine D3 receptor (D3R) is a proven therapeutic target for the treatment of neurological and neuropsychiatric disorders. In particular, D3R-selective ligands that can eliminate side effects associated with dopamine D2 receptor (D2R) therapeutics have been validated. However, the high homology in signaling pathw...

journal_title：MedChemComm

authors： Cao Y,Sun N,Zhang J,Liu Z,Tang YZ,Wu Z,Kim KM,Cheon SH

更新日期：2018-06-14 00:00:00

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

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