ARTICLE | doi:10.20944/preprints202101.0571.v1
Online: 27 January 2021 (16:35:15 CET)
In the pursuit of better treatments, the concept of a chemically-active material, responding to local conditions by causing reactions, or reacting to produce substances that are deemed beneficial, seems laudable. Ultimately, the goal appears to be to recruit natural biological processes such that a natural ‘repair’ is effected. This goal seems to be the reason for prefixing “bio-“ to many terms with a view to advertising the desire, yet without presenting evidence that it has occurred, or indeed that it is capable of occurring, relying instead on non-biological processes to justify the claims. The dogma is such that all work where local ‘responsive’ chemistry is involved must receive the label “bioactive” to legitimize and promote. Nevertheless, the primary evidence adduced is flawed, and the claim must fail. A rethink to restore scientific sense and confidence in the endeavour is essential if real progress is to be made.
ARTICLE | doi:10.20944/preprints202105.0459.v1
Subject: Life Sciences, Biochemistry Keywords: bioactivity; phytochemistry; cytostatic, cytotoxicity; microalga
Online: 20 May 2021 (09:11:44 CEST)
New resources of food, pharmaceuticals or biotechnological products are needed. The huge biodiversity of aero-terrestrial lichen-symbiont microalgae remains unexplored. Viability of these for human consumption demands the demonstration of the absence of toxic effects. In vitro biocompatibility of crude homogenates of axenic microalga Asterochloris erici, symbiotic in the lichen Cladonia cristatella, was analyzed after treatment of cultured L929 fibroblasts with different doses of microalgal homogenates. The results show that crude homogenates of A. erici do not induce fibroblast cytotoxicity but seem to have some cytostatic effect inducing slight cell cycle alterations and intracellular reactive oxygen species (ROS) increase at the highest dose. Carotenoid analysis demonstrates high content of lutein, a xanthophyll with antioxidant and cytostatic properties in vivo. These findings confirm that Asterochloris erici can be considered suitable for the development of alimentary or pharmaceutical applications. The cytostatic effects should be further investigated for antitumor agents.
REVIEW | doi:10.20944/preprints201802.0051.v1
Subject: Life Sciences, Biotechnology Keywords: metals; dental regeneration; bioactivity; tissue regeneration; bone
Online: 6 February 2018 (05:25:46 CET)
The regeneration of bone tissue is a main purpose of most therapies in dental medicine. For bone regeneration, calcium phosphate (CaP)-based substitute materials based on natural (allo- and xenografts) and synthetic origins (alloplastic materials) are applied for guiding the regeneration processes. The optimal bone substitute has to act as a substrate for bone ingrowth into a defect, while it should be resorbed even in the time frame needed for complete regeneration up to the condition of restitution ad integrum. In this context, the modes of action of CaP-based substitute materials have been frequently investigated and it has been shown that such materials strongly influence regenerative processes such as osteoblast growth or differentiation and also on osteoclastic resorption due to different physicochemical properties of the materials. However, the material characteristics needed for the required ratio between the formation of new bone tissue and material degradation has not been found until now. The addition of different substances such as collagen or growth factors and also of different cell types have already been tested but did not allow for sufficient or prompt application. Moreover, metals or metal ions are differently used as basis or as supplement for different materials in the field of bone regeneration. Moreover, it has already been shown that different metal ions are integral components of bone tissue playing functional roles in the physiological cellular environment as well as in the course of bone healing. The present review focuses on frequently used metals as integral parts of materials designated for bone regeneration with the aim to give an overview of currently existing knowledge about the effects of metals in the field of bone regeneration.
REVIEW | doi:10.20944/preprints202204.0271.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Annonaceae; Annona; custard apple; phytochemistry; bioactivity; pharmacological activity
Online: 28 April 2022 (04:16:02 CEST)
In 1789, the Annonaceae family was cataloged by de Jussieu. It encompasses tropical and subtropical plants which are widespread in distribution across various continents such as Asia, South and Central America, Australia and Africa. The genus of Annona is one of the 120 genera of the Annonaceae family and contains more than 119 species of trees and shrubs. The majority of these species are found in tropical America with more than 105 species (26 of them are endemic). Due to its edible fruits and medicinal properties, Annona is the most important genus of Annonaceae family. Despite Annona having many species, only limited species of this family are economically important such as A. squamosa L. (sugar apple), A. cherimola Mill. (Cherimoya), A. muricata L. (guanabana or soursop), A. atemoya Mabb. (atemoya), a hybrid between A. cherimola and A. squamosa, A. reticulata L. (custard apple), A. glabra L. (pond-apple) and A. macroprophyllata Donn. Sm. (ilama). Phytochemically, several classes of secondary metabolites such as acetogenins, essential oils, alkaloids, terpenoids and flavonoids have been described in this genus. A variety of pharmacological activities have been reported from various parts of Annona species specially leaves and seeds including applications against antibacterial, anticancer, antidiabetic and anti-inflammatory.
ARTICLE | doi:10.20944/preprints202011.0611.v1
Subject: Life Sciences, Biochemistry Keywords: cyanobacteria; thermal mud; natural products; anti-inflammatory; bioactivity
Online: 24 November 2020 (10:53:33 CET)
Background: The Balaruc-les-Bains’ thermal mud was found to be colonized predominantly by microorganisms, with cyanobacteria constituting the primary organism in the microbial biofilm observed on the mud surface. The success of cyanobacteria in colonizing this specific ecological niche can be explained in part by their taxa-specific adaptation capacities, and also the diversity of bioactive natural products that they synthesize. This array of components has physiological and ecological properties that may be exploited for various applications.
REVIEW | doi:10.20944/preprints201810.0487.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: bioactivity; essential oils; polyphenols; preclinical; rosmarinic acid; terpeniods
Online: 22 October 2018 (10:09:22 CEST)
Perilla frutescens (L.) Britt. (PF) is an annual herbal medicinal, aromatic, functional food and ornamental plant that belongs to the mint family, Lamiaceae. The origin of perilla traces back to East Asian countries (China, Japan, Korea, Taiwan, Vietnam and India), where it has been used as a valuable source of culinary and traditional medicinal uses. Leaves, seeds and stems of P. frutescens are used for various therapeutic applications in folk medicine. In the absence of comprehensive review regarding all aspects of perilla, thus this review aims to present an overview pertaining to the botanical drug, ethnobotany, phytochemistry and biological activity. It was found that the taxonomic classification of perilla species is quite confused, and the number of species is vague. Perilla has traditionally been prescribed to treat depression-related disease, anxiety, asthma, chest stuffiness, vomiting, cough, cold, flus, phlegm, tumour, allergy, intoxication, fever, headache, stuffy nose, constipation, abdominal pain, indigestion, analgesic, anti-abortive agent, and sedative. Until now, 271 natural molecules have been identified in perilla organs including; polyphenols, flavonoids, essential oils, triterpenes, carotenoids, phytosterols, fatty acids, tocopherols and policosanols. In addition to solvent extracts, these individual compounds (rosmarinic acid, perillaldehyde, luteolin, apigenin, tormentic acid, isoegomaketone) have attracted researchers' interest for pharmacological properties. Its bioactivity showed antioxidant, antimicrobial, anti-allergic, antidepressant, anti-inflammatory, anticancer, neuroprotection activity. Although the results are promising in preclinical studies (in vitro and in vivo) as well, clinical studies are insufficient, therefore further study needs to be done to validate its therapeutic effects and to ensure its safety and efficacy.
ARTICLE | doi:10.20944/preprints202012.0453.v1
Subject: Biology, Anatomy & Morphology Keywords: Actinidia arguta; leaf; bioactivity; antioxidant activity; LC-MS/MS
Online: 18 December 2020 (11:14:24 CET)
Actinidia arguta (Sieb. et Zucc.) Planch. ex Miq. is abundant of vitamin C and bioactive compounds with high antioxidant activities. In this study, eight wild A. arguta accessions from different areas in Northeast China were collected. Some bioactive compounds were examined on the different tissues of different germplasms including four kinds of leaves, petioles and fruits. The method of UPLC-MS was used to detect the flavonoid compounds. The results showed that some bioactive compounds including vitamin C, soluble sugar, free amino acid, total phenolics and flavonoids content showed significant differences between six tissues of A. arguta accessions and showed significant variability with maturity. In eight accessions, the highest vitamin C content was found in young apical leaves of ‘CBS-6’ (7.47 mg/g fresh weight), and the highest soluble sugar content was in fruits of ‘CJ-1’ (196.52 mg/g fresh weight) and the highest total phenolic content and total flavonoids content were in young apical leaves of ‘CBS-11’ (3.48 mg/g fresh weight) and of ‘CBS-3’ (2.00 mg/g fresh weight), respectively. Ten flavonoid compounds including kaempferol, isorhamnetin and quercetin were detected in leaves, petioles and fruits. The total content of flavonoids were highest in young apical leaves (10219.84 µg·g-1) and the lowest in fruits (78.75 µg·g-1). Based on the comparison of the contents of several bioactive compounds, the two accessions ‘CJ-1’ and ‘CBS-8’ had relatively outstanding performance, and in the comprehensive evaluation of the antioxidant activity among different tissues, the young leaves had the strongest antioxidant activity. These results highlighted the antioxidant potentialities of A. arguta leaves as a major source of phenolics and vitamin C as well as flavonoids. It provided a theoretical basis for the utilization of leaves of A. arguta.
REVIEW | doi:10.20944/preprints201906.0029.v1
Subject: Chemistry, Organic Chemistry Keywords: antitumour compounds; marine natural products; bioactivity; cytotoxicity; marine invertebrates
Online: 4 June 2019 (12:55:33 CEST)
Recent advances in sampling and novel techniques in drug synthesis and isolation have promoted the discovery of anticancer agents from marine organisms to combat this major threat to public health worldwide. Bryozoans, filter-feeding, sessile aquatic invertebrates often characterized by a calcified skeleton, are an excellent source of pharmacologically interesting compounds including well-known chemical classes such as alkaloids and polyketides. This review covers the literature for secondary metabolites isolated from marine cheilostome and ctenostome bryozoans that have shown potential as cancer drugs. Moreover, we highlight examples such as bryostatins, the most known class of marine-derived compounds from this animal phylum, which is advancing through anticancer clinical trials due to their low toxicity and antineoplastic activity. The bryozoan antitumour compounds discovered until now show a wide range of chemical diversity and biological activities. Therefore, more research focusing on the isolation of secondary metabolites with potential anticancer properties from bryozoans and other overlooked taxa covering wider geographic areas is needed for an efficient bioprospecting of natural products.
ARTICLE | doi:10.20944/preprints202102.0245.v1
Subject: Materials Science, Biomaterials Keywords: Mesoporous Bioactive Glass Nanopartciles; Sol-Gel; Antibacterial Activity; Silver; Bioactivity
Online: 10 February 2021 (07:54:28 CET)
Biomedical implants are the need of this era due to the increase in number of accidents and follow-up surgeries. Different types of bone diseases such as osteoarthritis, osteomalacia, bone cancer, etc. are increasing globally. Mesoporous bioactive glass nanoparticles (MBGNs) are used in biomedical devices due to their osteointegration and bioactive properties. In this study, silver (Ag) and strontium (Sr) doped mesoporous bioactive glass nanoparticles (Ag-Sr MBGNs) were prepared by a modified Stöber process. In this method, Ag+ & Sr2+ were co-substituted in pure MBGNs to harvest the antibacterial properties of Ag ions, as well as pro-osteogenic potential of Sr2 ions. The effect of the two ion concentration on morphology, surface charge, composition, antibacterial ability, and in-vitro bioactivity was studied. Scanning electron microscopy (SEM), X-Ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) confirmed the doping of Sr and Ag in MBGNs. SEM and EDX analysis confirmed the spherical morphology and typical composition of MBGNs, respectively. The Ag-Sr MBGNs showed a strong antibacterial effect against Staphylococcus carnosus and Escherichia coli bacteria determined via turbidity and disc diffusion method. Moreover, the synthesized Ag-Sr MBGNs develop apatite-like crystals upon immersion in simulated body fluid (SBF), which suggested that the addition of Sr improved in-vitro bioactivity. The Ag-Sr MBGNs synthesize in this study can be used for the preparation of scaffolds or as a filler material in the composite coatings for bone tissue engineering.
ARTICLE | doi:10.20944/preprints202105.0308.v1
Subject: Biology, Anatomy & Morphology Keywords: Indonesia; biodiversity; novel antibiotics; drug screening; bioactivity; gene cluster networking; GNPS
Online: 13 May 2021 (14:05:00 CEST)
Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two-thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Besides, eight putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.
ARTICLE | doi:10.20944/preprints202208.0103.v1
Subject: Chemistry, Medicinal Chemistry Keywords: Resveratrol; antioxidant metabolism; scavengome; biomimetic oxidation; bioactivity-guided isolation; NMR spectroscopy; xanthine oxidase
Online: 4 August 2022 (05:33:52 CEST)
Resveratrol is a well-known natural polyphenol with a plethora of pharmacological activities. As a potent antioxidant, resveratrol is highly oxidizable, and readily reacts with reactive oxygen species (ROS). Such a reaction not only leads to a decrease in ROS levels in a biological environ-ment but may also generate a wide range of metabolites with altered bioactivities. Inspired by this notion, in the current study, our aim was to take a diversity-oriented chemical approach to study the chemical space of oxidized resveratrol metabolites. Chemical oxidation of resveratrol and a bioactivity-guided isolation strategy using xanthine oxidase (XO) and radical scavenging activities led to the isolation of a diverse group of compounds, including a chlorine-substituted compound (2), two iodine-substituted compounds (3 and 4), two viniferins (5 and 6), an eth-oxy-substituted compound (7) two ethoxy-substituted dimers (8 and 9). Compounds 4, 7, 8 and 9 are reported here for the first time. All compounds without ethoxy-substitution exerted stronger XO inhibition than their parent compound, resveratrol. By enzyme kinetic and in silico docking studies compounds 2, 3 and 4 were identified as potent competitive inhibitors of the enzyme while the viniferins acted as mixed-type inhibitors. Further, compounds 2 and 9 had better DPPH scavenging activity and oxygen radical absorbing capacity than resveratrol. Our results suggest that the antioxidant activity of resveratrol is modulated by the effect of a cascade of chemically stable oxidized metabolites, several of which have significantly altered target specificity as compared to their parent compound.
REVIEW | doi:10.20944/preprints202108.0249.v1
Subject: Materials Science, Biomaterials Keywords: whitlockite; calcium magnesium phosphates; struvite; newberrite; bone reconstruction; resorba-bility; bioactivity; orthopedic applications
Online: 11 August 2021 (10:41:43 CEST)
ARTICLE | doi:10.20944/preprints201907.0194.v1
Subject: Materials Science, Biomaterials Keywords: Cuttlefish bone; Biphasic calcium phosphate; Porous scaffolds; Sol-gel coatings; Bioactivity; Tissue engineering
Online: 16 July 2019 (12:32:14 CEST)
The combination of calcium phosphates (CaP) with bioactive glasses (BG) has received an increased interest in the field of bone tissue engineering. In the present work, biphasic calcium phosphates (BCP) obtained by hydrothermal transformation (HT) of cuttlefish bone (CB) were coated with a Sr-, Mg- and Zn-doped sol-gel derived BG. The scaffolds were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The initial CB structure was maintained after HT and the scaffold functionalization did not jeopardize the internal structure. The results of in vitro bio-mineralization after immersing the BG coated scaffolds in simulated body fluid (SBF) showed extensive formation of bone-like apatite onto the surface of the scaffolds. Overall, the functionalized CB derived BCP scaffolds revealed promising properties for their use in bone tissue engineering field.
ARTICLE | doi:10.20944/preprints202008.0690.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: Theopapuamides A-D; Virtual Screening; Chemoinformatics; Conceptual DFT; Computational Peptidology; Bioavailability; Bioactivity Scores; ADMET
Online: 31 August 2020 (03:57:38 CEST)
This work presents the results of a computational study of the chemical reactivity and bioactivity properties of the members of the Theopapuamides A-D family of marine peptides by making use of our own proposed methodology named Computational Peptidology (CP) that has been successfully considered in previous studies of this kind of molecular systems. CP allowed for the determination of the global and local descriptors that come from Conceptual Density Functional Theory (CDFT) that can give an idea of the chemical reactivity properties of the marine natural products under study which are already known to be related to their bioactivity. At the same time, the validity of the procedure based on the adoption of the KID (Koopmans in DFT) technique as well as the MN12SX/Def2TZVP/H2O model chemistry has been successfully verified. Together with several Chemoinformatic tools that can be used for the improvement of process of Virtual Screening, some additional properties of these marine peptides were identified related to their ability to behave as useful drugs. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) parameters related to the Theopapuamides A-D pharmacokinetics are also reported.
REVIEW | doi:10.20944/preprints202110.0354.v1
Subject: Chemistry, Organic Chemistry Keywords: Phorbas; marine sponges; marine natural products (MNPs); bioactivity,; cytotoxic metabolites; antimicrobial and anti-inflammatory activities; sesterterpene
Online: 25 October 2021 (13:16:55 CEST)
Porifera, commonly referred to as marine sponges, have stood out as major producers of marine natural products (MNPs). Sponges of the genus Phorbas have attracted much attention along years. They are widespread in all continents, and several structurally unique compounds have been identified from species of this genus. Terpenes, mainly sesterterpenoids, represent the great majority of secondary metabolites isolated from Phorbas species, even though several alkaloids and steroids have also been reported. Many of these compounds have shown a variety of biological activities. Particularly, Phorbas sponges have been demonstrated to be a source of cytotoxic metabolites. In addition, MNPs exhibiting cytostatic, antimicrobial and anti-inflammatory activities, have been isolated and structurally characterized. This work brings an overview of Phorbas secondary metabolites reported since the first study published in 1993 until 2020, and their biological activities.
REVIEW | doi:10.20944/preprints202008.0223.v1
Subject: Chemistry, Inorganic & Nuclear Chemistry Keywords: Serum transferrin; endocytosis; nonferric metal ions; metal transport, bioavailability, and bioactivity; metal therapeutic function and toxicity
Online: 9 August 2020 (21:47:51 CEST)
Serum transferrin (sTf) plays a pivotal role in regulating iron biodistribution and homeostasis within the body. The molecular details of sTf Fe(III) binding, blood transport, and cellular delivery through transferrin receptor-mediated endocytosis are generally well-understood. Emerging interest exists in exploring sTf complexation of nonferric metals as it facilitates the therapeutic potential and toxicity of several of them. This review explores recent X-ray structural and physiologically relevant metal speciation studies to understand how sTf partakes in the bioactivity of key non-redox active hard Lewis acidic metals. It challenges preconceived notions of sTf structure function correlations that were based exclusively on the Fe(III) model by revealing distinct coordination modalities that nonferric metal ions can adopt and different modes of binding to metal-free and Fe(III)-bound sTf that can directly influence how they enter into cells and, ultimately, how they may impact human health. This knowledge informs on biomedical strategies to engineer sTf as a delivery vehicle for metal-based diagnostic and therapeutic agents in the cancer field. It is the intention of this work to open new avenues for characterizing the functionality and medical utility of nonferric-bound sTf and to expand the significance of this protein in the context of bioinorganic chemistry.
ARTICLE | doi:10.20944/preprints202008.0351.v1
Subject: Chemistry, General & Theoretical Chemistry Keywords: discodermins A-H; chemical reactivity theory; conceptual DFT; global and local reactivity descriptors; pKa; bioavailability; bioactivity scores; ADME
Online: 17 August 2020 (04:45:58 CEST)
A methodology based on the concepts that arise from Density Functional Theory named Conceptual Density Functional Theory (CDFT) was chosen for the calculation of some global and local reactivity descriptors of the Discodermins A-H family of marine peptides through the consideration of the KID (Koopmans in DFT) technique that was successfully used in previous studies of this kind of molecular systems. The determination of active sites of the studied molecules for different kind of reactivities was achieved by resorting to some CDFT-based descriptors like the Fukui functions as well as the Parr functions derived from Molecular Electron Density Theory (MEDT). A few properties identified with their ability to behave as a drug and the bioactivity of the peptides considered in this examination were acquired by depending on a homology model by studying the correlation with the known bioactivity of related molecules in their interaction with various biological receptors. With the further object of analyzing their bioactivity some parameters of usefulness for future QSAR studies, their predicted biological targets and the the ADME (Absorption, Distribution, Metabolism, and Excretion) parameters related to the Discodermins A-H pharmacokinetics are also reported.