Microwave-Assisted Synthesis, Structural Characterization and Assessment of the Antibacterial Activity of Some New Aminopyridine, Pyrrolidine, Piperidine and Morpholine Acetamides.

A series of new acetamide derivatives 22-28 of primary and secondary amines and para-toluene sulphinate sodium salt have been synthesized under microwave irradiation and assessed in vitro for their antibacterial activity against one Gram-positive and two Gram-negative bacterial species such as S. pyogenes, E. coli, and P. mirabilis using the Mueller-Hinton Agar diffusion (well diffusion) method. The synthesized compounds with significant differences in inhibition diameters and MICs were compared with those of amoxicillin, ampicillin, cephalothin, azithromycin and doxycycline. All of the evaluated acetamide derivatives were used with varying inhibition concentrations of 6.25, 12.5, 37.5, 62.5, 87.5, 112.5 and 125 µg/mL. The results show that the most important antibacterial properties were displayed by the synthetic compounds 22 and 24, both of bear a para-chlorophenyl moiety incorporated into the 2-position moiety of acetamide 1. The molecular structures of the new compounds were determined using the FT-IR and 1H-NMR techniques.

Photoactivation of MDM2 Inhibitors: Controlling Protein-Protein Interaction with Light.

Selectivity remains a major challenge in anticancer therapy, which potentially can be overcome by local activation of a cytotoxic drug. Such triggered activation can be obtained through modification of a drug with a photoremovable protecting group (PPG), and subsequent irradiation in the chosen place and time. Herein, the design, synthesis and biological evaluation is described of a photoactivatable MDM2 inhibitor, PPG-idasanutlin, which exerts no functional effect on cellular outgrowth, but allows for the selective, noninvasive activation of antitumor properties upon irradiation visible light, demonstrating activation with micrometer, single cell precision. The generality of this method has been demonstrated by growth inhibition of multiple cancer cell lines showing p53 stabilization and subsequent growth inhibition effects upon irradiation. Light activation to regulate protein-protein interactions between MDM2 and p53 offers exciting opportunities to control a multitude of biological processes and has the potential to circumvent common selectivity issues in antitumor drug development.

Raphanusanin-mediated resistance to pathogens is light dependent in radish and Arabidopsis thaliana.

Raphanusanin (Ra) is a light-induced inhibitor of hypocotyl growth that responds to unilateral blue light illumination in radish seedlings. We have previously shown that Ra regulates genes that are involved in common defense mechanisms. Many genes that are induced by Ra are also positively regulated by early blue light. To extend the understanding of the role of Ra in pathogen defense, we evaluated the effects of Ra on radish and Arabidopsis thaliana (A. thaliana) infected with the necrotrophic pathogen Botrytis cinerea (B. cinerea) and biotrophic pathogen Pseudomonas syringae (P. syringae). Radish and A. thaliana were found to be resistant to both pathogens when treated with Ra, depending on the concentration used. Interestingly, Ra-mediated resistance to P. syringae is dependent on light because Ra-treated seedlings exhibited enhanced susceptibility to P. syringae infection when grown in the dark. In addition to regulating the biotic defense response, Ra inhibited seed germination and root elongation and enhanced the growth of root hairs in the presence of light in radish and A. thaliana. Our data suggest that Ra regulates the expression of a set of genes involved in defense signaling pathways and plays a role in pathogen defense and plant development. Our results show that light may be generally required not only for the accumulation of Ra but also for its activation during the pathogen defense response.

Synthesis and characterization of novel soluble fulleropyrrolidine derivatives and their photovoltaic performance.

Currently, [60] fullerene derivatives are the focus of considerable research due to their important roles in many fields, especially material science. In this study, we synthesized the following two novel fulleropyrrolidine derivatives: C60-fused N-methyl-(4-hexyloxybenzen-2-yl) pyrrolidine, (p-HOPF) and C60-fused N-methyl-(2-hexyloxybenzen-2-yl) pyrrolidine, (o-HOPF). Structural assignments of the two fullerene derivatives were made through 1H NMR and FAB-MS. We also measured the optical and electrochemical properties of p-HOPF and o-HOPF through UV/Vis spectrophotometry and cyclic voltammetry. We found that the difference in the position of the alkoxyl substituent on the phenyl ring greatly affects the characteristics of the molecules. In particular, from the 1H NMR spectrum, we found that the hydrogen atoms on the carbons adjacent to the oxygens in p-HOPF and o-HOPF have completely different chemical environments. In order to study the effects of the substituent group positions on photovoltaic performance, photovoltaic devices were fabricated. The highest power conversion efficiency, 0.71%, was achieved when using o-HOPF as the electron acceptor.

[60]Fulleropyrrolidines bearing π-conjugated moiety for polymer solar cells: contribution of the chromophoric substituent on C60 to the photocurrent.

Two fullerene-terthiophene dyads without hexyl chains (3T-C60) and with hexyl chains (3TH-C60) on the terthiophene substituent are synthesized by 1,3-dipolar cycloaddition of corresponding azomethine ylides to C60. The cyclic voltammetry studies indicate no apparent electronic communication between the terthiophene pendent group and the fulleropyrrolidine core in the ground state. However, a significant florescence quenching is observed for 3T-C60 and 3TH-C60, compared to their fluorescent terthiophene (3T) and 3TH precursors, respectively, suggesting the occurrence of strong intramolecular electron/energy transfers in the photoexcited state. Furthermore, these new fulleropyrrolidine derivatives are applied as electron acceptors to fabricate poly(3-hexylthiophene) (P3HT) based bulk heterojunction solar cells. The incident photon-to-current efficiency (IPCE) value of the P3HT/3T-C60 device is significantly higher than that of the P3HT/PCBM cell in wavelengths of 350-420 nm. This finding provides direct evidence for the contribution of 3T excitons to the photocurrent. Replacing 3T-C60 with 3TH-C60 effectively improves the morphology of the photoactive layer and widens the window of optimal D/A ratios, raising the power conversion efficiency (PCE) from 2.14% to 2.54%. Importantly, these devices exhibit superior stability of PCE against high-temperature aging.

Raphanusanin-induced genes and the characterization of RsCSN3, a raphanusanin-induced gene in etiolated radish hypocotyls.

Raphanusanin is a light-induced growth inhibitor involved in inhibition of hypocotyl growth in response to unilateral blue light illumination in radish seedlings. To understand better the role of raphanusanin in growth inhibition, we randomly analyzed raphanusanin-induced genes using a modified DD-RT-PCR (differential display RT-PCR) approach. The differential expression RT-PCR approach resulted in identification of four known candidate genes, of which three encoded functional proteins known to be related to responsiveness to diverse environmental stimuli. One of these genes appeared to be an essential element in the inhibition of hypocotyl growth, and was named RsCSN3 (a homologue of subunit 3 of the COP9 signalosome). During the growth inhibition that was observed within minutes of irradiation, the expression of the RsCSN3 gene was increased by phototropic stimulation, as well as by raphanusanin treatment, suggesting that this gene is involved in light-induced growth inhibition. In addition, down-regulation of the RsCSN3 transcript, that is specifically expressed at 60 min after the onset of stimulation under blue light, green light, and raphanusanin treatment, shows a functional correlation with the phototropic response.

Pathophysiological significance of in vivo ESR signal decay in brain damage caused by X-irradiation. Radiation effect on nitroxyl decay of a lipophilic spin probe in the head region.

X-irradiation of mice decreased the decay rate of the in vivo ESR signal in the head region to 75% of the control when 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-yloxy (MCPROXYL), a lipophilic and blood-brain barrier-permeable spin probe, was used. We attempted to identify the specific factor responsible for the decrease in the signal decay rate caused by X-irradiation. The signal decay of MCPROXYL in the head region depends on the following three factors: (1) blood concentration of MCPROXYL, (2) reduction to the corresponding hydroxylamine in the brain tissue, and (3) effusion of MCPROXYL from the brain tissue. Irradiation at 15 Gy did not significantly change the rate of decrease of blood concentration of MCPROXYL at 1 h post-irradiation. The reducing activity of the brain homogenate was not changed by the X-irradiation (15 Gy). The contents of MCPROXYL and its hydroxylamine derivative in the brain of 15 Gy-irradiated mice remained higher than in non-irradiated mice. These findings suggest that the effect of X-irradiation observed by in vivo ESR is attributable not to the redox reaction of MCPROXYL in the brain but to the change of the efflux rate of the MCPROXYL from the brain.

Radiolysis of spin-labeled DNA: an electron spin resonance investigation.

The reactions of free and DNA-bound 2,2,5,5-tetramethylpyrrolidine-N-oxyl (PROXYL) probes with radicals generated during radiolysis of dilute aqueous solutions of DNA were examined. For the free PROXYL probe in deaerated solution with each of the four nucleotides (dAMP, dCMP, dGMP, and TMP) it was found that the pyrimidine radicals were more reactive toward the probe than were the purine radicals. Reactions of the electron adduct of TMP and the hydroxyl radical adducts of dAMP, dGMP, and TMP with the probe resulted in little or no reduction of the probe. For TMP these results are consistent with the fact that both the protonated electron and hydroxyl radical adducts of TMP will covalently bind to the nitroxide function of the probe. Reduction of the PROXYL probe was observed in reactions with the hydroxyl radical adduct of dCMP and with the electron adducts of dAMP, dCMP, and dGMP. Results of the radiolysis of the free PROXYL probe in deaerated dilute solution of DNA suggest that the PROXYL probe protects the DNA from water radical attack as the ratio of DNA bases to PROXYL probe increases above 50:1. Reactions of DNA-bound probes are dependent on the depth of the nitroxide function in relation to the major groove of the DNA helix. Two probes with tether lengths which are less than the depth of the major groove show an expected increase in reactions with DNA base radicals as compared to a probe with a tether that extends beyond the groove. The longer probe is involved largely in reactions with sugar and water radicals along the periphery of the DNA helix. In the presence of oxygen, there is a dramatic decrease in the loss of both the free and DNA-bound probes due to the lack of reaction of these probes with peroxyl radicals formed by the addition of molecular oxygen to DNA radicals.