A novel ditopic chemosensor for cadmium and fluoride and its possible application as a pH sensor

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.

Rational design, synthesis, and evaluation of novel 2,4-Chloro- and Hydroxy-Substituted diphenyl Benzofuro[3,2-b]Pyridines: Non-intercalative catalytic topoisomerase I and II dual inhibitor

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.


Mass spectrometry as a versatile ancillary technique for the rapid in situ identification of lichen metabolites directly from TLC plates

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.

Isolation and Structure Identification of Novel Brominated Diketopiperazines from Nocardia ignorata—A Lichen-Associated Actinobacterium

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.

Triple reuptake inhibitors: Design, synthesis and structure–activity relationship of benzylpiperidine–tetrazoles

Suresh Paddle, Xiao Min, Srijan Acharya, Seung Hoon Cheon

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.

Design, synthesis, and antimelanogenic effects of (2-substituted phenyl-1,3-dithiolan-4-yl)methanol derivatives

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.

Potassium Phthalimide (PPI): An Efficient and Green Organocatalyst for the One-pot Synthesis of 6-amino-1,4-dihydropyrano[2,3-c]-pyrazole-5- carbonitrile Derivatives under Microwave Irradiation

Rajesh H. Vekariya, Kinjal D. Patel, Neelam P. Prajapati, Hitesh D. Patel

Background: Potassium phthalimide (PPI), a mild, green and commercially available organocatalyst used in the synthesis of a wide range of important bioactive compounds. 6-amino-1,4- dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives were synthesized via a four component reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehydes and malononitrile by utilizing various homogenous as well as heterogeneous catalysts, which usually involve relatively lower product yields and prolonged reaction times. We describe a simple and straightforward protocol to prepare pyrano[2,3-c]-pyrazole derivatives that address these drawbacks.

Methods: Utilizing microwave irradiation (MWI) and with the use of water as a universal and green solvent, a series of 6-amino-1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives (5a-5o) have been efficiently prepared from the four component reaction of ethyl acetoacetate, hydrazine hydrate, aryl aldehydes and malononitrile.

Results: The reactions proceeded in short periods of time (3-4 min) without side products, affording the products in 91-97 % yields. Reactions under microwave conditions were faster than those achieved with conventional heating. Water showed better result compared to other organic solvents in terms of product yield and reaction time.

Conclusion: Short reaction times, mild reaction conditions, excellent product yields, use of inexpensive catalyst and easy work-up procedure and no use of toxic organic solvents are remarkable advantages of this approach. The discussed methodology can be applied to generate a variety of 6-amino- 1,4-dihydropyrano[2,3-c]-pyrazole-5-carbonitrile derivatives, which serve as precursors to compounds of pharmaceutical interest.

The MS analysis was carried out using Advion Expression® CMS.

Copper complexes containing thiosemicarbazones derived from 6-nitropiperonal: Antimicrobial and biophysical properties

Floyd A.Beckford, Kelsey R.Webb

A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49–7.50) × 104 M− 1. In relation to HSA, the complexes interact strongly with binding constants on the order of 105 M− 1. The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals. The antimicrobial profiles of the compounds, tested against a panel of microbes including five of the ESKAPE pathogens (Staphylococcus aureus, MRSA, Escherichia coli, Klebsiella pneumoniae, MDR, Acinetobacter baumannii, Pseudomonas aeruginosa) and two yeasts (Candida albicans and Cryptococcus neoformans var. grubii), are also described. The compounds contain a core moiety that is similar to oxolinic acid, a quinolone antibiotic that targets DNA gyrase and topoisomerase (IV). The binding interaction between the complexes and these important antibacterial targets were studied by computational methods, chiefly docking studies. The calculated dissociation constants for the interaction with DNA gyrase B (from Staphylococcus aureus) range from 4.32 to 24.65 μM; the binding was much stronger to topoisomerase IV, with dissociation constants ranging from 0.37 to 1.27 μM.

The MS analysis was carried out using Advion Expression® CMS.

Design, synthesis, and structure-activity relationship study of halogen containing 2-benzylidene-1-indanone derivatives for inhibition of LPS-stimulated ROS production in RAW 264.7 macrophages

Aarajana Shrestha, HyeJin Oh, Mi Jin Kim, Nirmala Tilija Pun, Til Bahadur Thapa Magar, Ganesh Bist, Hongseok Choi, Pil-Hoon Park, Eung-Seok Lee

As a continuous effort to discover new potential anti-inflammatory agents, we systematically designed and synthesized sixty-one 2-benzylidene-1-indanone derivatives with structural modification of chalcone, and evaluated their inhibitory activity on LPS-stimulated ROS production in RAW 264.7 macrophages. Systematic structure-activity relationship study revealed that hydroxyl group in C-5, C-6, or C-7 position of indanone moiety, and ortho-, meta-, or para-fluorine, trifluoromethyl, trifluoromethoxy, and bromine functionalities in phenyl ring are important for inhibition of ROS production in LPS-stimulated RAW 264.7 macrophages. Among all the tested compounds, 6-hydroxy-2-(2-(trifluoromethoxy) benzylidene)-2,3-dihydro-1H-inden-1-one (compound 44) showed the strongest inhibitory activity of ROS production. Further studies on the mode of action revealed that compound 44 potently suppressed LPS-stimulated ROS production via modulation of NADPH oxidase. The findings of this work could be useful to design 2-benzylidene-indanone based lead compounds as novel anti-inflammatory agents.

The MS analysis was carried out using Advion Expression® CMS.

Membrane-enclosed multienzyme (MEME) synthesis of 2,7-anhydro-sialic acid derivatives

Marie Monestier, Dimitrios Latousakis, Andrew Bell, Sandra Tribal, Louise E. Tailford, Ian J. Colquhoun, Gwenaelle Le Gall, Hai Yu, Xi Chen, Martin Rejzek, Simone Dedola, Robert A. Field, Nathalie Juge

Naturally occurring 2,7-anhydro-alpha-N-acetylneuraminic acid (2,7-anhydro-Neu5Ac) is a transglycosylation product of bacterial intramolecular trans-sialidases (IT-sialidases). A facile one-pot two-enzyme approach has been established for the synthesis of 2,7-anhydro-sialic acid derivatives including those containing different sialic acid forms such as Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). The approach is based on the use of Ruminoccocus gnavus IT-sialidase for the release of 2,7-anhydro-sialic acid from glycoproteins, and the conversion of free sialic acid by a sialic acid aldolase. This synthetic method, which is based on a membrane-enclosed enzymatic synthesis, can be performed on a preparative scale. Using fetuin as a substrate, high-yield and cost-effective production of 2,7-anhydro-Neu5Ac was obtained to high-purity. This method was also applied to the synthesis of 2,7-anhydro-Neu5Gc. The membrane-enclosed multienzyme (MEME) strategy reported here provides an efficient approach to produce a variety of sialic acid derivatives.

The MS analysis was carried out using Advion Expression® CMS ESI.