The design of a bioreversibly protected lipophilic sugar nucleotide as a potential membrane‐permeable precursor of adenosine diphosphate ribose (ADPR) is described. ADPR is the most potent activator of the transient receptor potential melastatin 2 (TRPM2) ion channel. Membrane‐permeable, lipophilic derivatives of ADPR are of great interest as tools for study of the mechanism of TRPM2. The approach described here was based on our recently disclosed “DiPPro” and “TriPPPro” prodrug approaches developed for the intracellular delivery of nucleotides. A lipophilic, bioreversibly masked ADPR analogue containing an enzymatically cleavable 4‐pentanoyloxybenzyl (PB) mask at the phosphate moiety next to the 5′‐position of adenosine, together with O‐acetyl groups, was prepared in high yields. Chemical and enzymatic hydrolysis studies in phosphate buffer (pH 7.3) were performed to assess chemical stability and possible (selective) enzymatic demasking of the ADPR analogue. HPLC‐MS revealed that the PB group was readily cleaved enzymatically. In addition, the formation of partially deacetylated ADPR compounds and also of fully unprotected ADPR was observed.
The MS analysis was carried out using Advion Expression® CMS.
J. A. H. Inkster, S. Zhang, V. Akurathi, A. Belanger, S. Dubey, S. T. Treves, A. B. Packard
New chemical and radiochemical syntheses are described for the preparation of [18F]Rho6G-DEG-F, an 18F-labeled analogue of the fluorescent dye rhodamine 6G, which has shown promise as myocardidal perfusion imaging agent. Tosylated precursors of [18F]Rho6G-DEG-F amenable to 18F-labeling were obtained either through a two-step synthesis from rhodamine 6G lactone (33% yield), or in one step from rhodamine 575 (64% yield), then purified by preparative C18 chromatography. Manual synthesis of [18F]Rho6G-DEG-F was achieved in a single radiochemical step from either the tosylate salt or the tosylate/formate double salt in DMSO under standard nucleophillic aliphatic 18F-fluorination conditions (K[18F]F/K2CO3/Kryptofix 2.2.2.). Incorporation of the [18F]F− was found to be satisfactory (≥34% by TLC), despite the protic character of the precursor molecules. [18F]Rho6G-DEG-F was manually synthesized in final decay-corrected radiochemical yields of 11–26% (tosylate salt) and 9–21% (tosylate/formate double salt). The protocol was transferred to an automated synthesis unit, where the product was obtained in 3–9% radiochemical yield (n = 3) decay corrected to start-of-synthesis, >99% radiochemical purity, and a molar activity of 122–267 GBq μmol−1 (3.3–7.2 Ci μmol−1).
The MS analysis was carried out using Advion Expression® CMS.
Eun Kyeong Lee, Ju Hyun Kim, Kyoung Mi Moon, Sugyeong Ha, Sang-Gyun Noh, Dae Hyun Kim, Bonggi Lee, Do Hyun Kim, Su Jeong Kim, Sultan Ullah, Hyung Ryong Moon, Hae Young Chung
The inhibition of tyrosinase, a key enzyme in mammalian melanin synthesis, plays an important role in preventing skin pigmentation and melanoma. Therefore, tyrosinase inhibitors are very important in the fields of medicine and cosmetics. However, only a few tyrosinase inhibitors are currently available because of their toxic effects on skin or lack of selectivity and stability. Therefore, we synthesized a novel series of (E)-2-(substituted benzylidene)-2,3-dihydro-1H-cyclopenta[a]naphthalen-1-one derivatives and evaluated their inhibitory effects on mushroom tyrosinase, with the aim of discovering a novel tyrosinase inhibitor. Among 19 derivatives, MHY3655 ($IC_{50}
The MS analysis was carried out using Advion Expression® CMS.
The Touch Express™ Open Port Sampling Interface (OPSI), is designed for simple sampling of solids, liquids and sample preparation tips and fibers. The novel ambient sampling technique was developed by Gary Van Berkel and Vilmos Kertesz, of Oak Ridge National Laboratory.
Paired with the electrospray ion source of the expression® Compact Mass Spectrometer, the product incorporates a low volume, open port of continuously swept solvent, flowing directly into the electrospray ion source of the mass spectrometer.
Additi Roy Chowdhury, Pritan Ghosh, Suparna Paul, Samuzal Bhuyan, Jagadeesh C. Bose K, Sudit Mukhopadhyay, Priyabrata Banerjee
A urea-based BPC [1,5-bis(perfluorophenyl)carbonohydrazide] molecule with four acidic NH protons has been synthesized by a facile synthetic process. The molecule was found to be a ditopic chemosensor for Cd2+ and F− ions. BPC was synthesized from low-cost starting materials, dinitrophenyl hydrazine and triphosgene. The host–guest interactions between the ions (Cd2+ and F−) were not only confirmed by convenient spectroscopic techniques such as UV-Vis, PL, 1H-NMR, FT-IR, and cyclic voltammetry but also through modern DFT, the results of which were in good agreement with the experimental results. In vitro studies in human cancer cells (HeLa cells) were successfully performed with BPC and Cd2+ using fluorescence microscopy. The reversible UV-Vis response for BPC with F−, OH− and H+ mimics multiple logic functions and can be used for several complex electronic circuits based on logic operations. The pH sensor (BPC) can be further interfaced with suitable circuitry interfaced with appropriate programming for ease of access and enhancement of its practical applications.
The MS analysis was carried out using Advion Expression® CMS.
Seojeong Park, Til Bahadur Thapa Magar, Tara Man Kadayat, Hwa Jong Lee, Ganesh Bist, Aarajana Shrestha, Eung-Seok Lee, Youngjoo Kwon
Novel series of conformationally constrained 2,4-chloro- and hydroxy-substituted diphenyl benzofuro[3,2-b]pyridines were rationally designed and synthesized. Their biological activities were evaluated for topoisomerase I and II inhibitory activity, and antiproliferative activity against several human cancer cell lines for the development of novel anticanceragents. Most of the compounds with phenol moiety at 4-position of central pyridine exhibited significant dual topoisomerase I and II inhibitory activities, and strong antiproliferative activity in low micromolar range. Structure activity relationship study suggested that phenol moiety at 4-position of the central pyridine regardless of chlorophenyl moiety at 2-position of the central pyridine has an important role in dual topoisomerase inhibitory activity as well as antiproliferative activity. For investigation of mode of action for compound 14 which displayed the most strong dual topoisomerase I and II inhibitory activity and antiproliferative activity against HCT15 cell, we performed cleavable complex assay, band depletion assay, comet assay, and competitive EtBr displacement assay. Compound 14 functioned as non-intercalative catalytic topo I and II dual inhibitor. In addition, compound 14 induced apoptosisin HCT15 cells through increase of Bax, decrease of Bcl-2 and increase of PARP cleavage.
The MS analysis was carried out using Advion Expression® CMS.
Pierre Le Pogam, Aline Pillot, Françoise Lohezic-le Devehat, Anne-Cécile Le Lamer, Béatrice Legouin, Alice Gadea, Aurélie Sauvager, Damien Ertz, Joël Boustie
Thin-layer chromatography (TLC) still enjoys widespread popularity among lichenologists as one of the fastest and simplest analytical strategies, today remaining the primary method of assessing the secondary product content of lichens. The pitfalls associated with this approach are well known as TLC leads to characterizing compounds by comparison with standards rather than properly identifying them, which might lead to erroneous assignments, accounting for the long-held interest in hyphenating TLC with dedicated identification tools. As such, commercially available TLC/Mass Spectrometry (MS) interfaces can be easily connected to any brand of mass spectrometer without adjustments. The spots of interest are extracted from the TLC plate to retrieve mass spectrometric signals within one minute, thereby ensuring accurate identification of the chromatographed substances. The results of this hyphenated strategy for lichens are presented here by 1) describing the TLC migration and direct MS analysis of single lichen metabolites of various structural classes, 2) highlighting it through the chemical profiling of crude acetone extracts of a set of lichens of known chemical composition, and finally 3) applying it to a lichen of unknown profile, Usnea trachycarpa.
The TLC/MS analysis was carried out using Advion Expression® CMS + Plate Express.
Alba Noël,Solenn Ferron, Isabelle Rouaud,Nicolas Gouault, Jean-Pierre Hurvois, Sophie Tomasi
Actinobacteria are well known for their potential in biotechnology and their production of metabolites of interest. Lichens are a promising source of new bacterial strains, especially Actinobacteria, which afford a broad chemical diversity. In this context, the culture medium of the actinobacterium Nocardia ignorata, isolated from the terrestrial lichen Collema auriforme, was studied. The strain was cultivated in a BioFlo 115 bioreactor, and the culture medium was extracted using an XAD7HP resin. Five known diketopiperazines: cyclo (l-Pro-l-OMet) (1), cyclo (l-Pro-l-Tyr) (2), cyclo (d-Pro-l-Tyr) (3), cyclo (l-Pro-l-Val) (4), cyclo (l-Pro-l-Leu) (5), and one auxin derivative: indole-carboxaldehyde (8) were isolated, along with two new brominated diketopiperazines: cyclo (d-Pro-l-Br-Tyr) (6) and cyclo (l-Pro-l-Br-Tyr) (7). Structure elucidation was performed using HRMS and 1D and 2D NMR analysis, and the synthesis of compounds 6 and 7 was carried out in order to confirm their structure.
The MS analysis was carried out using Advion Expression® CMS.
Monoamine transporters are important targets in the treatment of various central nervous disorders. Several limitations of traditional reuptake inhibitors, like delayed onset of action, insomnia, and sexual dysfunction, have compelled the search for safer, more effective compounds. In this study, we have sought to identify novel monoamine reuptake inhibitors. Based upon the docking study of compounds that we had reported previously, aromatic rings (A1) were modified to generate a novel series of benzylpiperidine-tetrazoles. Thirty-one compounds were synthesized and evaluated for their triple reuptake inhibition of serotonin, norepinephrine and dopamine. Triple reuptake inhibitor, compound 2q, in particular, showed potent serotonin reuptake inhibition, validating our design approach.
The MS analysis was carried out using Advion Expression® CMS ESI.
Do Hyun Kim, Su Jeong Kim, Sultan Ullah, Hwi Young Yun and Pusoon Chun, Hyung Ryong Moon
The authors designed and synthesized 17 (2-substituted phenyl-1,3-dithiolan-4-yl) methanol (PDTM) derivatives to find a new chemical scaffold, showing excellent tyrosinase-inhibitory activity. Their tyrosinase-inhibitory activities were evaluated against mushroom tyrosinase at 50 μM, and five of the PDTM derivatives (PDTM3, PDTM7–PDTM9, and PDTM13) were found to inhibit mushroom tyrosinase more than kojic acid or arbutin, the positive controls. Of seventeen PDTMs, PDTM3 (half-maximal inhibitory concentration 13.94±1.76 μM), with a 2,4-dihydroxyphenyl moiety, exhibited greatest inhibitory effects (kojic acid half-maximal inhibitory concentration 18.86±2.14 μM). Interestingly, PDTM compounds with no hydroxyl group, PDTM7–PDTM9, also had stronger inhibitory activities than kojic acid. In silico studies of interactions between tyrosinase and the five PDTMs suggested their binding affinities were closely related to their tyrosinase-inhibitory activities. Cell-based experiments performed using B16F10 mouse-skin melanoma cells showed that PDTM3 effectively inhibited melanogenesis and cellular tyrosinase activity. A cell-viability study conducted using B16F10 cells indicated that the antimelanogenic effect of PDTM3 was not attributable to its cytotoxicity. Kinetic studies showed PDTM3 competitively inhibited tyrosinase, indicating binding to the tyrosinase-active site. We found that PDTM3 with a new chemical scaffold could be a promising candidate for skin-whitening agents, and that the 1,3-dithiolane ring could be used as a chemical scaffold for potent tyrosinase inhibition.
The MS analysis was carried out using Advion Expression® CMS.
