Synthesis and characterization of tributyltin derivatives from 4‐oxo‐4‐(arylamino)butanoic acids and their in vitro biological activity against cervical cancer cell lines

Uterine (cervix and corpus) cancer is one of the major causes of mortality in women in Mexico. Organotin carboxylated derivatives have shown high cytotoxic activity against various cell lines of human origin. We describe the synthesis of three new tri‐n‐butyltin derivatives from 4‐oxo‐4‐(arylamino)butanoic acids; their structures were confirmed using spectral data (¹H NMR, ¹³C NMR, ¹¹⁹Sn NMR and infrared), elemental analyses, mass spectrometry and X‐ray diffraction. All the tri‐n‐butyltin carboxylates exhibit ¹ J (^119/117Sn–¹³C) coupling satellites in solution and lie in the range 357 to 339 Hz, suggesting a tetrahedral geometry around the tin atom. The polymeric structures of two of the derivatives and the monomeric structure of another were confirmed using X‐ray crystallography. Using succinic anhydride as raw material, five N‐substituted succinamic acid compounds were synthesized by the acylation reaction with aniline, 4‐nitroaniline, 4‐nitro‐3‐(trifluoromethyl)aniline, 2‐amino‐5‐nitrothiazole and 4‐aminoantipyrine. From these compounds, five tin derivatives were prepared and their in vitro anti‐proliferative effect on HeLa, CaSki and ViBo cell lines was screened. All of the compounds showed potency against all three strains and null or low cytotoxic activity (necrotic) as well. The most potent of our derivatives as an anti‐proliferative agent against the three cell lines was tributylstannyl 4‐oxo‐4‐[(3‐trifluoromethyl‐4‐nitrophen‐1‐yl)amino]butanoate, exhibiting an IC₅₀ value of 0.43 μM against the HeLa cell line. Copyright © 2014 John Wiley & Sons, Ltd.     

Toxicological Screening of Four Bioactive Citroflavonoids: In Vitro,In Vivo,and In Silico Approaches

Many studies describe different pharmacological effects of flavonoids on experimental animals and humans. Nevertheless, few ones are confirming the safety of these compounds for therapeutic purposes. This study aimed to investigate the preclinical safety of naringenin, naringin, hesperidin, and quercetin by in vivo, in vitro, and in silico approaches. For this, an MTT-based cytotoxicity assay in VERO and MDCK cell lines was performed. In addition, acute toxicity was evaluated on Wistar rats by OECD Guidelines for the Testing of Chemicals (Test No. 423: Acute Oral Toxicity-Class Method). Furthermore, we used the ACD/Tox Suite to predict toxicological parameters such as hERG channel blockade, CYP450 inhibition, and acute toxicity in animals. The results showed that quercetin was slightly more cytotoxic on cell lines (IC₅₀ of 219.44 ± 7.22 mM and 465.41 ± 7.44 mM, respectively) than the other citroflavonoids. All flavonoids exhibited an LD₅₀ value > 2000 mg/kg, which classifies them as low-risk substances as OECD guidelines established. Similarly, predicted LD⁵⁰ was LD₅₀ > 300 to 2000 mg/kg for all flavonoids as acute toxicity assay estimated. Data suggests that all these flavonoids did not show significant toxicological effects, and they were classified as low-risk, useful substances for drug development.     

Vibrational Spectra of Arsenates and Phosphates of the Type Kcaln(XO4)2

The infrared and Raman spectra of polycrystal-line samples of different compounds of the types KCaLn(AsO₄)₂ and KCaLn(PO₄)₂, belonging to the hexagonal LaPO₄, structural modification, were recorded and discussed. A complete vibrational assignment, based on a factor group analysis, is proposed. The influence of the different lanthanide cations on the internal vibrations of the XO₄ groups is briefly discussed and some comparisons with related compounds are also made.

It is well known that simple lanthanide arsenates, phosphates, vanadates and cnromates (V) of the type LnXO₄ belong to two different structural types.     

Communicative Suitability of Voice Following Radiotherapy for T1 Glottic Carcinoma: Testing the Reliability of a Rating Instrument

The objective of the study was to determine whether a communicative suitability rating instrument could be used in a meaningful way to assess functionality of voice following radiotherapy for T1 glottic cancer. Seventeen naive listeners judged the suitability of voice of a patient group with T1 glottic carcinoma (n = 20) just before treatment, a group of patients (n = 40) after radiotherapy, and a matched control group (n = 20) of normal speakers. Listeners rated suitability on a 10-point scale for 10 speaking situations, which supposedly make different demands. In order to validate scores on communicative suitability, ratings were related to perceptual voice quality evaluations and videolaryngostroboscopic evaluations. Results indicate that the concept of measuring listener judgments of communicative suitability of voice is basically sound. Raters are reliable and can discriminate between groups of normal and pathological voices. Patients with T1 glottic carcinoma (assessed before the start of treatment) have on average the least suitable voices. Following radiotherapy suitability is, on average, improved, but does not approach the suitability of normal voices. Ratings on communicative suitability were clearly related to perceptual voice quality aspects and videolaryngostroboscopic evaluations. A subset of three communicative suitability rating scales is recommended as part of the protocol for evaluating voice outcome after radiotherapy for early glottic cancer, besides perceptual evaluation of voice quality by trained and naive raters, videolaryngostroboscopy, acoustical analyses, and self-ratings of vocal performance.     

GridMass: a fast two‐dimensional feature detection method for LC/MS

One of the initial and critical procedures for the analysis of metabolomics data using liquid chromatography and mass spectrometry is feature detection. Feature detection is the process to detect boundaries of the mass surface from raw data. It consists of detected abundances arranged in a two‐dimensional (2D) matrix of mass/charge and elution time. MZmine 2 is one of the leading software environments that provide a full analysis pipeline for these data. However, the feature detection algorithms provided in MZmine 2 are based mainly on the analysis of one‐dimension at a time. We propose GridMass, an efficient algorithm for 2D feature detection. The algorithm is based on landing probes across the chromatographic space that are moved to find local maxima providing accurate boundary estimations. We tested GridMass on a controlled marker experiment, on plasma samples, on plant fruits, and in a proteome sample. Compared with other algorithms, GridMass is faster and may achieve comparable or better sensitivity and specificity. As a proof of concept, GridMass has been implemented in Java under the MZmine 2 environment and is available at http://bioinformatica.mty.itesm.mx/GridMass and MASSyPup. It has also been submitted to the MZmine 2 developing community. Copyright © 2015 John Wiley & Sons, Ltd.     

Chemical Diversity and Biological Activity of Secondary Metabolites Isolated from Indonesian Marine Invertebrates

Marine invertebrates have been reported to be an excellent resource of many novel bioactive compounds. Studies reported that Indonesia has remarkable yet underexplored marine natural products, with a high chemical diversity and a broad spectrum of biological activities. This review discusses recent updates on the exploration of marine natural products from Indonesian marine invertebrates (i.e., sponges, tunicates, and soft corals) throughout 2007–2020. This paper summarizes the structural diversity and biological function of the bioactive compounds isolated from Indonesian marine invertebrates as antimicrobial, antifungal, anticancer, and antiviral, while also presenting the opportunity for further investigation of novel compounds derived from Indonesian marine invertebrates.     

Sensitivity enhancement using chemically reactive gas cluster ion beams in secondary ion mass spectrometry (SIMS)

We report for the first time on significant molecular secondary ion yield increases by modifying the chemistry of a water cluster primary ion beam. This was demonstrated using 70-keV ion beams of 0.15 eV/amu. For the neutral drug Bezafibrate, secondary ion yield enhancements ×5–10 were observed when replacing the Ar carrier gas in a water gas cluster ion beam (GCIB) source with a mixture containing 12% CO₂ and 2% O₂ in Ar. For the cationic drug Ranitidine, the ion yield enhancements using the CO₂-containing carrier gas were up to ×20–50 in positive mode and ×2–4 in negative mode. The extent of molecular fragmentation was very similar from both cluster beams. We conclude that additional chemically reactive species are present in the impact zone using the (H₂O/CO₂)_n projectile, which promote the formation of secondary ions of both polarity through projectile impact-induced chemical reactions. This methodology can be applied to further extend the capabilities of high-resolution 3-dimensional mass spectral imaging using reactive GCIB-SIMS.     

Chiroptical Properties – Structure Relationship in Bicyclic Isoxazolidin‐5‐one Derivatives

The relationship between chiroptical properties of substituted bicyclic isoxazolidin‐5‐one derivatives and their molecular structures was investigated. The chromophoric system in isoxazolidinones was found to be nonplanar with a shallow pyramidal configuration at the N‐atom. The deviation from planarity can be attributed to the strain imposed by the bicyclic skeleton. Due to the nonplanarity, the isoxazolidinone system becomes inherently dissymmetric, which is supported by the high magnitude of the CD band occurring around 210 nm. In addition, the helicity of lactone moiety in investigated bicyclic isoxazolidinones is controlled by the absolute configuration at C(6). On this basis, a helicity rule correlating a positive (negative) helicity expressed by the OC(8) O(9) N(1) torsional angle with a positive (negative) sign of the CD band around 210 nm was formulated.