Abstract：
:Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired damage. This encouraged us to exploit the more acidic pH of cancerous tissue and design pH-controllable singlet oxygen-generating boron-dipyrromethene (BODIPY) dyes. A pH sensitivity of the dyes is achieved by the introduction of an electronically decoupled, photoinduced electron transfer (PET)-capable subunit in meso-position of the BODIPY core. To favor triplet-state formation as required for singlet oxygen generation, iodine substituents were introduced at the chromophore core. The resulting pH-controlled singlet oxygen-generating dyes with pKa values in the physiological range were subsequently assessed regarding their potential as pH-controlled PS for PDT. Using HeLa cells, we could successfully demonstrate markedly different pH-dependent cytotoxicities upon illumination.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Radunz S,Wedepohl S,Röhr M,Calderón M,Tschiche HR,Resch-Genger Udoi
10.1021/acs.jmedchem.9b01873subject
Has Abstractpub_date
2020-02-27 00:00:00pages
1699-1708issue
4eissn
0022-2623issn
1520-4804journal_volume
63pub_type
杂志文章abstract：:Novel substituted benzoyl benzoic acids and phenylacetic acids 1-14 have been synthesized and evaluated for inhibition of rat and human steroid 5alpha-reductase isozymes 1 and 2. The compounds turned out to be potent and selective human type 2 enzyme inhibitors, exhibiting IC(50) values in the nanomolar range. The phe...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm050728w
更新日期：2006-01-26 00:00:00
abstract：:The optimization of a series of aminooxazoline xanthene inhibitors of β-site amyloid precursor protein cleaving enzyme 1 (BACE1) is described. An early lead compound showed robust Aβ lowering activity in a rat pharmacodynamic model, but advancement was precluded by a low therapeutic window to QTc prolongation in cardi...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm501266w
更新日期：2014-12-11 00:00:00
abstract：:A novel lysine-based trifunctional chelate 3 was designed, synthesized, and characterized and bears both a chelating moiety (CHX-A' ') for sequestering radiometals (86Y or 111In) and the near-infrared dye Cy5.5 for dual modality PET (or SPECT) and fluorescence imaging, respectively. Successful conjugation of 3 to the ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070657w
更新日期：2007-09-20 00:00:00
abstract：:We report two crystal structures of the PARP domain of human tankyrase-2 (TNKS2). Tankyrases are involved in fundamental cellular processes such as telomere homeostasis and Wnt signaling. The complex of TNKS2 with the potent inhibitor XAV939 provides insights into the molecular basis of the strong interaction and sugg...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm100249w
更新日期：2010-07-22 00:00:00
abstract：:We have previously determined that Ac-D-Trp-Leu-Asp-Ile-Ile-Trp (peptide I), an endothelin antagonist, binds specifically (Ki = 1.9 microM) to the rat pituitary gonadotropin-releasing hormone (GnRH) receptor. Moreover, peptide I exhibits a GnRH agonistic activity, mediated directly by the GnRH receptor. We now report ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990432o
更新日期：2000-07-27 00:00:00
abstract：:Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00004a008
更新日期：1995-02-17 00:00:00
abstract：:Analogues of luliberin containing an alpha-azaamino acid in position 6, 9, or 10 (I--XIV) have been synthesized by the solution method of peptide synthesis. Two nonaza analogues, [D-Phe6]- and [D-Ser(But)6,des-Gly-NH2(10),Pro-ethylamide9]luliberin, were also synthesized for comparison. The ovulation-inducing activity ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00208a004
更新日期：1978-10-01 00:00:00
abstract：:Selective inhibition of neuronal nitric oxide synthase (nNOS) has been shown to prevent brain injury and is important for the treatment of various neurodegenerative disorders. This study shows that not only greater inhibitory potency and isozyme selectivity but more druglike properties can be achieved by fragment hopp...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm801220a
更新日期：2009-02-12 00:00:00
abstract：:The transcription factor nuclear factor kappaB (NF-kappaB), which regulates expression of numerous antiinflammatory genes as well as genes that promote development of the prosurvival, antiapoptotic state is up-regulated in many cancer cells. The natural product resveratrol, a polyphenolic trans-stilbene, has numerous ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm060630x
更新日期：2006-11-30 00:00:00
abstract：:The ester methyl [4-[2-[(2-hydroxy-3-phenoxypropyl)amino]ethoxy]phenoxy]acetate (1) (R1 = OMe) had previously been identified as the most interesting member of a series of selective beta 3-adrenergic agonists of brown adipose tissue and thermogenesis in the rat. In vivo it acts mainly via the related acid 1 (R1 = OH)....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00088a010
更新日期：1992-05-15 00:00:00
abstract：:Sulfur mustard (SM) is a highly toxic chemical warfare agent. A satisfactory treatment regimen is not yet available for this toxicant. In a search for an effective antidote against SM, a series of novel S-2(omega-aminoalkylamino)ethyl alkyl/aryl thioethers [H(2)N(CH(2))(n)()NHCH(2)CH(2)SR], where R = alky, alicyclic, ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030099v
更新日期：2004-07-15 00:00:00
abstract：:Two products without phosphoryl groups, 1-O-octadecyl-2-O-acetyl-3-O-[gamma-(dimethylamino)propyl]glycerol and its quaternary salt, were synthesized from 1-O-octadecyl-2-O-benzylglycerol. In comparison with PAF-acether, they lost aggregating and bronchoconstrictive activities and did not show any antagonistic effects....
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00146a019
更新日期：1985-08-01 00:00:00
abstract：:Ribonucleotide reductase (RR), an established cancer target, is usually inhibited by antimetabolites, which display multiple cross-reactive effects. Recently, we discovered a naphthyl salicyl acyl hydrazone-based inhibitor (NSAH or E-3a) of human RR (hRR) binding at the catalytic site (C-site) and inhibiting hRR rever...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.7b00530
更新日期：2018-02-08 00:00:00
abstract：:A novel series of ligands with substitutions at the 5-position on phenyl ring A and at the 4'-position on phenyl ring B of 2-(2'-((dimethylamino)methyl)-4'-(fluoroalkoxy)phenylthio)benzenamine (4'-2-fluoroethoxy derivatives 28-31 and 4'-3-fluoropropoxy derivatives 40-42) were prepared and tested as serotonin transport...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm070685e
更新日期：2007-12-27 00:00:00
abstract：:Selective CCK-A agonist activity has been reported to induce satiety in a variety of animals, including man, and thereby suggests a therapeutic role for CCK in the management of obesity. To date, three general classes of CCK-A agonists have been reported, the full-length, sulfated hepta- and hexapeptides, a series of ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990252e
更新日期：2000-06-15 00:00:00
abstract：:It is now plausible to dock libraries of 10 million molecules against targets over several days or weeks. When the molecules screened are commercially available, they may be rapidly tested to find new leads. Although docking retains important liabilities (it cannot calculate affinities accurately nor even reliably ran...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.5b02008
更新日期：2016-05-12 00:00:00
abstract：:A series of analogues of streptonigrin, in which the quinoline of ring B is replaced by isoquinoline and the substituted pyridine of ring C is replaced by phenyl, nitrophenyl, aminophenyl, or benzyl functions, have been prepared. Thus, 1-substituted isoquinoline-5,8-diones with 7-amino or 6-(alkylamino) groups were pr...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00110a018
更新日期：1991-06-01 00:00:00
abstract：:From the whole plant of Euphorbia peplus L., five new diterpenes based on a jatrophane skeleton (pepluanins A-E, 1-5) were isolated, together with two known analogues (6 and 7), which served to divulge in detail the structure-activity relationships within this class of P-glycoprotein inhibitors. The results revealed t...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030951y
更新日期：2004-02-12 00:00:00
abstract：:A series of D-erythro- and L-threo-ceramide analogues was synthesized and investigated for their ability to reverse the inhibitory effects of fumonisin B(1) (FB(1)) on axonal growth in hippocampal neurons. The analogues contained either a C(7) side chain or a phenyl group substituted for the C(13) residue present in n...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm990091e
更新日期：1999-07-15 00:00:00
abstract：:Desformylflustrabromine (dFBr; 1), perhaps the first selective positive allosteric modulator of α4β2 neuronal nicotinic acetylcholine (nACh) receptors, was deconstructed to determine which structural features contribute to its actions on receptors expressed in Xenopus ooycytes using two-electrode voltage clamp techn...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm200834x
更新日期：2011-10-27 00:00:00
abstract：:At present, the legendary magic bullet, i.e., a drug with high potency and selectivity toward a specific biological target, shares the spotlight with an emerging and alternative polypharmacology approach. Polypharmacology suggests that more effective drugs can be developed by specifically modulating multiple targets. ...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/jm5006463
更新日期：2014-10-09 00:00:00
abstract：:Inosine monophosphate dehydrogenase (IMPDH) is a key enzyme that is involved in the de novo synthesis of purine nucleotides. Novel 2-aminooxazoles were synthesized and tested for inhibition of IMPDH catalytic activity. Multiple analogues based on this chemotype were found to inhibit IMPDH with low nanomolar potency. O...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm0105777
更新日期：2002-05-23 00:00:00
abstract：:In an analogy to the potent catechol dopamine D1 agonists dihydrexidine (1) and dinapsoline (2), benzo rings were fused onto the structures of the dopamine D2-selective agonists quinelorane (3) and quinpirole (4). Each of the phenyl ring-substituted derivatives had significant affinity for D2 receptors, albeit somewha...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm9804533
更新日期：1999-03-11 00:00:00
abstract：:In pursuit of truncated glucagon analogues that can interact with the glucagon receptor with substantial binding affinity, 23 truncated glucagon analogues have been designed and synthesized. These truncated analogues consist of several fragments of glucagon with 11 or 12 amino acid residues (1-4), conformationally con...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm000453e
更新日期：2001-04-26 00:00:00
abstract：:A series of new peroxisome proliferator activated receptors (PPARs) chiral ligands have been designed following the accepted three-module structure comprising a polar head, linker, and hydrophobic tail. The majority of the ligands incorporate the oxazolidinone moiety as a novel polar head, and the nature of the hydrop...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.5b00849
更新日期：2015-08-27 00:00:00
abstract：:Although there is a significant effort in the design of a selective CDK9/CycT1 inhibitor, no compound has been proven to be a specific inhibitor of this kinase so far. The aim of this research was to develop novel and selective phosphorus containing CDK9/CycT1 inhibitors. Molecules bearing phosphonamidate, phosphonate...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm401742r
更新日期：2014-05-22 00:00:00
abstract：:The dopamine D4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D4, relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D4 antag...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章,评审
doi：10.1021/acs.jmedchem.7b00151
更新日期：2017-09-14 00:00:00
abstract：:Radiocopper-labeled pyruvaldehyde bis(N4-methylthiosemicarbazonato)copper(II), Cu[PTSM], is under investigation as a radiopharmaceutical for evaluation of regional blood flow in the brain, heart, and kidneys because it affords relatively high levels of radioactivity in these organs upon intravenous injection, followed...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm00168a035
更新日期：1990-06-01 00:00:00
abstract：:The synthesis and biological activities of four novel bispyridinium cyclophanes as choline kinase (ChoK) inhibitors are presented. Their synthetic methodology has been optimized according to dilution, temperature, and reaction time and provides pure bispyridinium cyclophanes in high yields very easily. One of these cy...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/jm030792i
更新日期：2003-08-14 00:00:00
abstract：:Macrophage elastase [matrix metalloproteinase (MMP)-12] is the most upregulated MMP in abdominal aortic aneurysm (AAA) and, hence, MMP-12-targeted imaging may predict AAA progression and rupture risk. Here, we report the design, synthesis, and evaluation of three novel hydroxamate-based selective MMP-12 inhibitors (CG...
journal_title：Journal of medicinal chemistry
pub_type： 杂志文章
doi：10.1021/acs.jmedchem.0c01514
更新日期：2020-12-10 00:00:00
