4-Thiophenyl-2-azetidinone as chiron: enantiospecific syntheses of 3R and 3S deuteriated β-alanines

Stereospecific syntheses of chirally C-3 deuteriated ß-alanines 6 and 7 from optically pure 4 - thiophenyl azetidinones 13 and 14 are described

A novel synthesis of β-lactam fused cyclic enediynes by intramolecular Kinugasa reaction

A general synthetic route to β-lactam-fused enediynes by intramolecular Kinugasa reaction has been successfully developed. The method has widened the scope of Kinugasa reaction in the synthesis of sensitive systems like the one described in this communication

Photoisomerization as a modulator of the DNA-cleaving efficiency of novel azo bispropargyl sulfones

Novel azobenzene based bispropargyl sulfones have been prepared in the thermally stable E-form: irradiation with a high-pressure Hg lamp converted them to the Z-isomer which showed higher DNA-cleaving efficiency

4-Benzoyloxy-2-azetidinone, a convenient synthon for β- lactam intermediates

4-Heterosubstituted-2-azetidenones were prepared in excellent yields from 4-benzoyloxy-2-azetidenone (4), a much cheaper and stabler substrate compared to more common 4-acetoxy-2- azetidenone (2)

Synthesis and reactivity of a 9-membered azaenediyne: importance of proximity effect in N-alkylation

Synthesis of a 9-membered azaenediyne has been achieved for the first time via intramolecular N-alkylation; the importance of proximity of the reacting centres via cobalt carbonyl complexation of the acetylenic moiety and not the activation of propargylic carbon has been demonstrated

Synthesis of β-lactam fused enediynes by intramolecular kinugasa reaction: comparison of reactivity with monocyclic analogues

β-lactam fused enediynes have been successfully synthesized by intramolecular Kinugasa reaction in moderate yields. DSC studies indicated significant influence of the β-lactam ring upon the reactivity of enediynes. None of the β-lactam fused enediynes (under ring opening conditions) as well as the 11-membered monocyclic enediyne as the tosylate salt showed any cleavage of plasmid DNA. Interestingly, the 10-membered enediyne as the tosylate salt cleaved both single and double strands of plasmid DNA at micromolar concentration

Nitrogen substituted cyclic enediynes: synthesis, thermal reactivity and complexation with metal ions

A number of N-substituted cyclic enediynes (azaenediynes) have been synthesized via Pd(0)-catalysed ene-yne coupling followed by N-alkylation. The simplest of them, a 10-membered monocyclic enediyne 1, underwent Bergman cyclization (BC) at 23°C with a half-life of 72 h. The kinetics of BC slowed down considerably by fusing a benzene ring onto the enediyne. Several novel bis(azaenediyne)s and bis(diazaenediyne)s 3-6 have been synthesized. Their onset temperatures for BC were lowered under metal ion complexation conditions

Chemistry of enediynyl azides: activation through a novel pathway

The spontaneous activation of a nonaromatic enediynyl azide under ambient conditions has been demonstrated. The aromatic enediyne followed the expected cycloaddition with the alkene in the neighbouring arm to form a stable bridged bicyclic enediyne

Glucose directly promotes antifungal resistance in the fungal pathogen, Candida spp

Effects of glucose on the susceptibility of antifungal agents are investigated against Candida spp. Increasing the concentration of glucose decreased the activity of antifungal agents, voriconazole was mostly affected drugs followed by amphotericin B. No significant change has been observed for anidulafungin. Biophysical interaction between antifungal agents with glucose molecules were investigated using ITC, FTIR and 1HNMR. Glucose have higher affinity to bind with voriconazole by hydrogen bonding and decrease the susceptibility. In addition to confirm the results observed in vitro, theoretical docking studies demonstrated that voriconazole presented three important hydrogen bonds and amphotericin B presented two hydrogen bonds that stabilized the complex compound-glucose. In vivo results also suggest that the physiologically relevant higher glucose level in blood stream of Diabetes Mellitus (DM) mice might interact with the available selective agents during antifungal therapy, decreased the activity by complex formation. Thus, selection of drugs for DM patient is important to control the infectious diseases

A Novel Enediynyl Peptide Inhibitor of Furin That Blocks Processing of proPDGF-A, B and proVEGF-C

BACKGROUND: Furin represents a crucial member of secretory mammalian subtilase, the Proprotein Convertase (PC) or Proprotein Convertase Subtilisin/Kexin (PCSK) superfamily. It has been linked to cancer, tumorgenesis, viral and bacterial pathogenesis. As a result it is considered a major target for intervention of these diseases. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we report, for the first time, the synthesis and biological evaluation of a newly designed potent furin inhibitor that contains a highly reactive beta-turn inducing and radical generating "enediynyl amino acid" (Eda) moiety. "Eda" was inserted between P1 and P1' residues of hfurin(98-112) peptide, derived from the primary cleavage site of furin's own prodomain. The resulting hexadecapeptide derivative inhibited furin in vitro with IC(50) approximately 40 nM when measured against the fluorogenic substrate Boc-RVRR-MCA. It also inhibited furin-mediated cleavage of a fluorogenic peptide derived from hSARS-CoV spike protein with IC(50) approximately 193 nM. Additionally it also blocked furin-processing of growth factors proPDGF-A, B and VEGF-C that are linked to tumor genesis and cancer. Circular dichroism study showed that this inhibitor displayed a predominantly beta-turn structure while western blots confirmed its ability to protect furin protein from self degradation. CONCLUSION/SIGNIFICANCE: These findings imply its potential as a therapeutic agent for intervention of cancer and other furin-associated diseases