Synthesis of jasplakinolide analogues containing a novel omega-amino acid

The synthesis of the omega-amino acid 4 is described utilizing a two-dimensional synthesis strategy combined with an enzymatic differentiation of homotopic ester groups. The amino acid 4 features two non-bonded interactions that result in conformational constraints on a cyclic construct. This amino acid was incorporated into the four macrolactams 17, 22, 31, and 37. The ring in 17 and 22 is 18-membered, whereas 31 and 37 have a 19-membered ring. The pairs with the same ring size differ in a N-methyl group. For the larger macrolactams (31 and 37) conformational analysis showed that the macrocyclic rings are somewhat more rigid than in the natural lead, the depsipeptide jasplakinolide. Nevertheless, their conformations are comparable to the natural product. There are no intramolecular hydrogen bonds, neither is the cis-rotamer populated in the N-methyl compound 37. Due to the increased flexibility of the smaller macrolactams 17 and 22 and signal overlap, a distinct solution structure could not be obtained for these compounds. The amino acid 4 should be useful for restricting the conformation of other small peptides.     

Conversion of Methane into Methanol and Ethanol over Nickel Oxide on Ceria–Zirconia Catalysts in a Single Reactor

The conversion of methane into alcohols under moderate reaction conditions is a promising technology for converting stranded methane reserves into liquids that can be transported in pipelines and upgraded to value‐added chemicals. We demonstrate that a catalyst consisting of small nickel oxide clusters supported on ceria–zirconia (NiO/CZ) can convert methane to methanol and ethanol in a single, steady‐state process at 723 K using O₂ as an abundantly available oxidant. The presence of steam is required to obtain alcohols rather than CO₂ as the product of catalytic combustion. The unusual activity of this catalyst is attributed to the synergy between the small Lewis acidic NiO clusters and the redox‐active CZ support, which also stabilizes the small NiO clusters.     

Synthesis and antimicrobial evaluation of some novel dithiolane,thiophene, coumarin,and 2-pyridone derivatives

Novel 2-cyano-N-[1-(naphtha-2-yl)ethylidene] acetohydrazide 1 was utilized as key intermediate for the synthesis of some new dithiolane, thiophene, coumarin, 2-pyridone, and other related products containing a hydrazide moiety. Newly synthesized compounds were characterized by elemental analyses and spectral data (IR, ¹H NMR and mass spectra). The antimicrobial activity of the synthesized compounds was evaluated.     

Sensitivity of in-Plane Strain Measurement to Calibration Parameter for out-of-Plane Specimen Rotations

In practice, out-of-plane motions usually are not avoidable during experiments. Since 2D–DIC measurements are vulnerable to parasitic deformations due to out-of-plane specimen motions, three-dimensional digital image correlation (StereoDIC or 3D–DIC) oftentimes is employed. The StereoDIC method is known to be capable of accurate deformation measurements for specimens subjected to general three-dimensional motions, including out-of-plane rotations and displacements. As a result, there has been limited study of the deformation measurements obtained when using StereoDIC to measure the displacement and strain fields for a specimen subjected only to out-of-plane rotation. To assess the accuracy of strain measurements obtained using stereovision systems and StereoDIC when a specimen undergoes appreciable out of plane rotation, rigid body out-of-plane rotation experiments are performed in the range ?40⁰?≤?θ?≤?40⁰ using a two-camera stereovision system. Results indicate that (a) for what would normally be considered “small angle” calibration processes, the measured normal strain in the foreshortened specimen direction due to specimen rotation increases in a non-linear manner with rotation angle, with measurement errors exceeding ±1400με and (b) for what would normally be considered “large angle” calibration processes, the magnitude of the errors in the strain are reduced to ±300με. To theoretically assess the effect of calibration parameters on the measurements, two separate analyses are performed. First, theoretical strains due to out-of-plane rigid body rotation are determined using a pinhole camera model to project a series of three-dimensional object points into the image plane using large angle calibration parameters and then re-project the corresponding sensor plane coordinates back into the plane using small angle calibration parameters. Secondly, the entire imaging process is also simulated in order to remove experimental error sources and to further validate the theory. Results from both approaches confirmed the same strain error trends as the experimental strain measurements, providing confidence that the source of the errors is the calibration process. Finally, variance based sensitivity analyses show that inaccuracy in the calibrated stereo angle parameter is the most significant factor affecting the accuracy of the measured strain.     

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

Ajuga bracteosa Wall. ex Benth. is an endangered medicinal herb traditionally used against different ailments. The present study aimed to create new insight into the fundamental mechanisms of genetic transformation and the biological activities of this plant. We transformed the A. bracteosa plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. These transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, elemental analysis, polyphenol content, and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was most abundant in all transgenic lines. Furthermore, transgenic line 3 (ABRL3) showed maximum phenolics and flavonoids content among all tested plant extracts. ABRL3 also demonstrated the highest total antioxidant capacity (8.16 ± 1 μg AAE/mg), total reducing power, (6.60 ± 1.17 μg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8 μg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 μg/mL), and iron-chelating power (IC50 = 154.8 ± 2 μg/mL). Moreover, transformed plant extracts produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant activities in BALB/c mice models. In conclusion, transgenic regenerants of A. bracteosa pose better antioxidant and pharmacological properties under the effect of rol genes as compared to wild-type plants.     

Synthetically Tuning the 2‐Position of Halogenated Quinolines: Optimizing Antibacterial and Biofilm Eradication Activities via Alkylation and Reductive Amination Pathways

Agents capable of eradicating bacterial biofilms are of great importance to human health as biofilm‐associated infections are tolerant to our current antibiotic therapies. We have recently discovered that halogenated quinoline (HQ) small molecules are: 1) capable of eradicating methicillin‐resistant Staphylococcus aureus (MRSA), methicillin‐resistant Staphylococcus epidermidis (MRSE) and vancomycin‐resistant Enterococcus faecium (VRE) biofilms, and 2) synthetic tuning of the 2‐position of the HQ scaffold has a significant impact on antibacterial and antibiofilm activities. Here, we report the chemical synthesis and biological evaluation of 39 HQ analogues that have a high degree of structural diversity at the 2‐position. We identified diverse analogues that are alkylated and aminated at the 2‐position of the HQ scaffold and demonstrate potent antibacterial (MIC≤0.39 μm ) and biofilm eradication (MBEC 1.0–93.8 μm ) activities against drug‐resistant Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecium strains while demonstrating <5 % haemolysis activity against human red blood cells (RBCs) at 200 μm . In addition, these HQs demonstrated low cytotoxicity against HeLa cells. Halogenated quinolines are a promising class of antibiofilm agents against Gram‐positive pathogens that could lead to useful treatments against persistent bacterial infections.