Structural Optimization and Improving Antitumor Potential of Moreollic Acid from Gamboge

Moreollic acid, a caged-tetraprenylated xanthone from Gamboge, has been indicated as a potent antitumor molecule. In the present study, a series of moreollic acid derivatives with novel structures were designed and synthesized, and their antitumor activities were determined in multifarious cell lines. The preliminary screening results showed that all synthesized compounds selectively inhibited human colon cancer cell proliferation. TH12-10, with an IC50 of 0.83, 1.10, and 0.79 μM against HCT116, DLD1, and SW620, respectively, was selected for further antitumor mechanism studies. Results revealed that TH12-10 effectively inhibited cell proliferation by blocking cell-cycle progression from G1 to S. Besides, the apparent structure–activity relationships of target compounds were discussed. To summarize, a series of moreollic acid derivatives were discovered to possess satisfactory antitumor potentials. Among them, TH12-10 displays the highest antitumor activities against human colon cancer cells, in which the IC50 values in DLD1 and SW620 are lower than that of 5-fluorouracil.

Towards Mapping of the Human Brain N-Glycome with Standardized Graphitic Carbon Chromatography

The brain N-glycome is known to be crucial for many biological functions, including its involvement in neuronal diseases. Although large structural studies of brain N-glycans were recently carried out, a comprehensive isomer-specific structural analysis has still not been achieved, as indicated by the recent discovery of novel structures with galactosylated bisecting GlcNAc. Here, we present a detailed, isomer-specific analysis of the human brain N-glycome based on standardized porous graphitic carbon (PGC)-LC-MS/MS. To achieve this goal, we biosynthesized glycans with substitutions typically occurring in the brain N-glycome and acquired their normalized retention times. Comparison of these values with the standardized retention times of neutral and desialylated N-glycan fractions of the human brain led to unambiguous isomer specific assignment of most major peaks. Profound differences in the glycan structures between naturally neutral and desialylated glycans were found. The neutral and sialylated N-glycans derive from diverging biosynthetic pathways and are biosynthetically finished end products, rather than just partially processed intermediates. The focus on structural glycomics defined the structure of human brain N-glycans, amongst these are HNK-1 containing glycans, a bisecting sialyl-lactose and structures with fucose and N-acetylgalactosamine on the same arm, the so-called LDNF epitope often associated with parasitic worms.

Co-option of the limb patterning program in cephalopod eye development

Background Across the Metazoa, similar genetic programs are found in the development of analogous, independently evolved, morphological features. The functional significance of this reuse and the underlying mechanisms of co-option remain unclear. Cephalopods have evolved a highly acute visual system with a cup-shaped retina and a novel refractive lens in the anterior, important for a number of sophisticated behaviors including predation, mating, and camouflage. Almost nothing is known about the molecular-genetics of lens development in the cephalopod. Results Here we identify the co-option of the canonical bilaterian limb patterning program during cephalopod lens development, a functionally unrelated structure. We show radial expression of transcription factors SP6-9/sp1, Dlx/dll, Pbx/exd, Meis/hth, and a Prdl homolog in the squid Doryteuthis pealeii, similar to expression required in Drosophila limb development. We assess the role of Wnt signaling in the cephalopod lens, a positive regulator in the developing Drosophila limb, and find the regulatory relationship reversed, with ectopic Wnt signaling leading to lens loss. Conclusion This regulatory divergence suggests that duplication of SP6-9 in cephalopods may mediate the co-option of the limb patterning program. Thus, our study suggests that this program could perform a more universal developmental function in radial patterning and highlights how canonical genetic programs are repurposed in novel structures.

Novel Structures of Functionalized Graphene Oxide with Hydrazide: Characterization and Bioevaluation of Antimicrobial and Cytocompatibility Features

Graphite was oxidized to graphene oxide and activated by thionyl chloride, for further covalently linking three hydrazides with potential biological activity. The obtained materials were characterized by scanning electron microscopy with energy dispersive spectroscopy, Fourier-transform infrared and Raman spectroscopies. The presence of various functional groups specific to graphene oxide (GO) functionalized with different hydrazides was confirmed by spectral data. The ratio between D- and G-bands, observed in Raman spectra, allowed for an evaluation of the disorder degree and the mean crystallite size of the samples. The micrographs highlighted that the samples lead to the occurrence of disorders, probably caused by the sp3 carbons, the formation of oxygen-containing functional groups in the basal planes, and by various structural defects. The new graphene oxide–hydrazide derivatives were tested for their antimicrobial and cytotoxicity activity. Their antimicrobial activity against planktonic and biofilm-embedded cells was inferior to that of free hydrazides, except for GO-3 against planktonic Escherichia coli and GO-2 against Pseudomonas aeruginosa biofilm, demonstrating that further optimization is needed to be able to exploit the huge potential of GO for developing potent antimicrobials.

Multi-Attribute Decision-Support System Based on Aggregations of Interval-Valued Complex Neutrosophic Hypersoft Set

Hypersoft set is an emerging field of study that is meant to address the insufficiency and the limitation of existing soft-set-like models regarding the consideration and the entitlement of multi-argument approximate function. This type of function maps the multi-subparametric tuples to the power set of the universe. It focuses on the partitioning of each attribute into its attribute-valued set that is missing in existing soft-set-like structures. This study aims to introduce novel concepts of complex intuitionistic fuzzy set and complex neutrosophic set under the hypersoft set environment with interval-valued settings. Two novel structures, that is, interval-valued complex intuitionistic hypersoft set (IV-CIFHS-set) and interval-valued complex neutrosophic hypersoft set (IV-CNHS-set), are developed via employing theoretic, axiomatic, graphical, and algorithmic approaches. After conceptual characterization of essential elementary notions of these structures, decision-support systems are presented with the proposal of algorithms to assist the decision-making process. The proposed algorithms are validated with the help of real-world applications. A comprehensive inter-cum-intra comparison of proposed structures is discussed with the existing relevant models, and their generalization is elaborated under certain evaluating features.

Novel Small-Molecule Hybrid-Antibacterial Agents against S. aureus and MRSA Strains

Ongoing resistance developments against antibiotics that also affect last-resort antibiotics require novel antibacterial compounds. Strategies to discover such novel structures have been dimerization or hybridization of known antibacterial agents. We found novel antibacterial agents by dimerization of indols and hybridization with carbazoles. They were obtained in a simple one-pot reaction as bisindole tetrahydrocarbazoles. Further oxidation led to bisindole carbazoles with varied substitutions of both the indole and the carbazole scaffold. Both the tetrahydrocarbazoles and the carbazoles have been evaluated in various S. aureus strains, including MRSA strains. Those 5-cyano substituted derivatives showed best activities as determined by MIC values. The tetrahydrocarbazoles partly exceed the activity of the carbazole compounds and thus the activity of the used standard antibiotics. Thus, promising lead compounds could be identified for further studies.

Structure Prediction and Mechanical Properties of Silicon Hexaboride on Ab Initio Level

Silicon borides represent very appealing industrial materials for research owing to their remarkable features, and, together with other boride and carbide-based materials, have very wide applications. Various Si–B phases have been investigated in the past, however a limited number of studies have been done on the pristine SiB6 compound. Structure prediction using a data mining ab initio approach has been performed in pure silicon hexaboride. Several novel structures, for which there are no previous experimental or theoretical data, have been discovered. Each of the structure candidates were locally optimized on the DFT level, employing the LDA-PZ and the GGA-PBE functional. Mechanical and elastic properties for each of the predicted and experimentally observed modifications have been investigated in great detail. In particular, the ductility/brittleness relationship, the character of the bonding, Young’s modulus E, bulk modulus B, and shear modulus K, including anisotropy, have been calculated and analyzed.

Sanitize It Yourself: Web-based molecular sanitization for machine-generated chemical structures

Many computer-aided drug design (CADD) methods using deep learning have recently been proposed to explore the chemical space toward novel scaffolds efficiently. However, there is a tradeoff between the ease of generating novel structures and the chemical feasibility of structural formulas. To overcome the limitations of computational filtering, we have implemented a web-based software in which users can share and evaluate computer-generated compounds. The web service is available at https://sanitizer.chemical.space/.

Brochosome-Inspired Metal-Containing Particles as Biomimetic Building Blocks for Nanoplasmonics: Conceptual Generalizations

Recently, biological nanostructures became an important source of inspiration for plasmonics, with many described implementations and proposed applications. Among them are brochosome-inspired plasmonic microstructures—roughly spherical core-shell particles with submicrometer diameters and with indented surfaces. Our intention was to start from the nanoplasmonic point of view and to systematically classify possible alternative forms of brochosome-inspired metal-containing particles producible by the state-of-the-art nanofabrication. A wealth of novel structures arises from this systematization of bioinspired metal-containing nanocomposites. Besides various surface nanoapertures, we consider structures closely related to them in electromagnetic sense like surface nano-protrusions, shell reliefs obtained by nano-sculpting, and various combinations of these. This approach helped us build a new design toolbox for brochosome-inspired structures. Additionally, we used the finite elements method to simulate the optical properties of simple brochosome-inspired structures. We encountered a plethora of advantageous optical traits, including enhanced absorption, antireflective properties, and metamaterial behavior (effective refractive index close to zero or negative). We conclude that the presented approach offers a wealth of traits useful for practical applications. The described research represents our attempt to outline a possible roadmap for further development of bioinspired nanoplasmonic particles and to offer a source of ideas and directions for future research.