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Journal of Natural Products Jun 2020Epipolythiodioxopiperazines (ETPs) are a class of biologically active fungal secondary metabolites characterized by a bridged polysulfide piperazine ring. Regularly, the...
Epipolythiodioxopiperazines (ETPs) are a class of biologically active fungal secondary metabolites characterized by a bridged polysulfide piperazine ring. Regularly, the sulfide functionality is attached in the α-positions of the dioxopiperazine scaffold. However, ETPs possessing irregular sulfur bridges have rarely been explored. This review summarizes that 83 compounds of this subtype have been isolated and characterized since the discovery of gliovirin in 1982. Herein, particular emphasis is given to the isolation, chemistry, and biological activity of this subtype. For a better understanding, a relevant summary focusing on the source microorganisms and their taxonomy is provided and will help elucidate the fascinating chemistry and biology of these unusual ETPs.
Topics: Anti-Bacterial Agents; Antibiotics, Antineoplastic; Bacteria; Eupenicillium; Fungi; Gliocladium; Humans; Jurkat Cells; Microbial Sensitivity Tests; Molecular Structure; Piperazines
PubMed: 32543845
DOI: 10.1021/acs.jnatprod.9b01283 -
Preparative Biochemistry & Biotechnology 2022In this study, four different nanofibers consisting of gelatin (Gel), doxorubicin (DOX) with gel (DOX@Gel), a composite of gel with poly(ethylene glycol)...
In this study, four different nanofibers consisting of gelatin (Gel), doxorubicin (DOX) with gel (DOX@Gel), a composite of gel with poly(ethylene glycol) (PEGylated-gel), and DOX@PEGylated-gel were fabricated. Subsequently, the nanofibers were thermally cross-linked in order to offer a stable and biocompatible alternative for the biological applications of nanofibers such as drug delivery and tissue engineering. Nanofibers were characterized by scanning electron microscopy, Fourier Transform-Infrared Spectroscopy (FT-IR), and confocal microscopy. The formation of smooth, continuous, and uniform nanofibers was observed and the addition of PEG resulted in an increase whereas the incorporation of DOX into nanofibers had no significant change in the diameter of nanofibers. Crosslinking also enlarged the diameter of all nanofibers and the most dramatic increase was observed 53% by DOX@PEGylated-gel. Afterward, the biological performance of the nanofibers was investigated by drug release profile, cytotoxicity on A549 cell line as well as antimicrobial activity with and . The results indicate an enhanced drug release profile, moderate antimicrobial activity, and reasonable cytotoxic efficiency for thermally cross-linked nanofibers compared to uncross-linked nanofibers.
Topics: A549 Cells; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Doxorubicin; Drug Carriers; Drug Delivery Systems; Escherichia coli; Gelatin; Humans; Nanofibers; Staphylococcus aureus
PubMed: 33775209
DOI: 10.1080/10826068.2021.1901232 -
Heart (British Cardiac Society) Nov 2020The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in...
OBJECTIVE
The aim of our study was to assess the association between risk of cancer-therapy-related cardiac dysfunction (CTRCD) after first follow-up and the difference in echocardiographic measures from baseline to follow-up.
METHODS
We retrospectively enrolled 87 consecutive patients (58±14 years, 55 women) who received anthracycline and underwent echocardiographic examinations both before (baseline) and after initial anthracycline administration (first follow-up). We measured absolute values of global longitudinal strain (GLS), apical longitudinal strain (LS), mid-LS and basal-LS at baseline and first follow-up, and per cent changes (Δ) of these parameters were calculated. Among 61 patients who underwent further echocardiographic examinations (second follow-up, third follow-up, etc), we assessed the association between regional left ventricular (LV) systolic dysfunction from baseline to follow-up and development of CTRCD, defined as LV ejection fraction (LVEF) under 53% and more absolute decrease of 10% from baseline, after first follow-up.
RESULTS
LVEF (65%±4% vs 63±4%, p=0.004), GLS (23.2%±2.6% vs 22.2±2.4%, p=0.005) and basal-LS (21.9%±2.5% vs 19.9±2.4%, p<0.001) at first follow-up significantly decreased compared with baseline. Among the 61 patients who had further follow-up echocardiographic examinations, 13% developed CTRCD. In the Cox-hazard model, worse Δbasal-LS was significantly associated with CTRCD. By Kaplan-Meier analysis, patients with Δbasal-LS decrease of more than the median value (-9.7%) had significantly worse event-free survival than those with a smaller decrease (p=0.015).
CONCLUSIONS
Basal-LS significantly decreased prior to development of CTRCD, and worse basal-LS was associated with development of CTRCD in patients receiving anthracycline chemotherapy.
Topics: Antibiotics, Antineoplastic; Cardiotoxicity; Echocardiography; Female; Follow-Up Studies; Heart Diseases; Humans; Male; Middle Aged; Neoplasms; Retrospective Studies; Risk Factors; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left
PubMed: 32209616
DOI: 10.1136/heartjnl-2019-316339 -
Colloids and Surfaces. B, Biointerfaces Sep 2019Keratin is a good candidate for drug carrier due to its good biocompatibility, low immunogenicity, redox responsiveness, and abundant renewable sources. Herein,...
Keratin is a good candidate for drug carrier due to its good biocompatibility, low immunogenicity, redox responsiveness, and abundant renewable sources. Herein, doxorubicin (DOX) was first conjugated with keratin through a pH-sensitive hydrazone linkage, and then prepared into particulate drug carrier via desolvation method. The size, morphology, and surface potential of keratin-DOX nanoparticles (KDNPs) were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The drug release results showed that KDNPs performed an excellent pH-sensitive behavior under acidic tumor microenvironment. Cytotoxicity assay by MTT confirmed that KDNPs exhibited the enhanced cytotoxicity against A549 cells. Furthermore, KDNPs had higher therapeutic efficiency in vivo than free DOX. Hemolysis assay indicated that KDNPs was blood compatible. All the results identified that KDNPs are well suited as an ideal drug carrier.
Topics: A549 Cells; Animals; Antibiotics, Antineoplastic; Cell Proliferation; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Screening Assays, Antitumor; Humans; Hydrogen-Ion Concentration; Injections, Intravenous; Keratins; Kinetics; Mice; Nanoparticles; Neoplasms, Experimental; Particle Size; Surface Properties
PubMed: 31382328
DOI: 10.1016/j.colsurfb.2019.06.057 -
Angewandte Chemie (International Ed. in... Feb 2022Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over...
Polymeric cylinders, a fascinating type of nanostructures with high surface area, internal volume and rigidity, have been exploited as novel drug delivery vehicles over the past decade. However, it's still an open challenge to afford cylindrical nanostructures using polymeric building blocks via traditional self-assembly processes. Herein, we report a hierarchical self-assembly strategy of preparing cylindrical aggregates (tubisomes) from an amphiphilic supramolecular bottlebrush polymer in which a cyclic peptide nanotube is employed as the noncovalent backbone. Additionally, an aggregation-induced emission (AIE) effect was introduced into the tubisomes to endow them with excellent fluorescent properties. Intriguingly, by encapsulating with the anticancer drug doxorubicin (DOX), both the fluorescence of tubisome and DOX can be quenched due to the energy transfer relay (ETR) effect. The release of DOX can induce the interruption of the ETR effect and recover the silenced fluorescence, thereby permitting the in-situ imaging of drug release. The AIE-featured supramolecular tubisomes reported here provide an alternative approach for fabricating cylindrical polymeric nanostructures and holds great potential for imaging-guided drug delivery.
Topics: Antibiotics, Antineoplastic; Doxorubicin; Drug Delivery Systems; Fluorescence; Humans; Macromolecular Substances; Nanostructures
PubMed: 34927320
DOI: 10.1002/anie.202115208 -
Artificial Cells, Nanomedicine, and... Dec 2019This paper aims to demonstrate the efficacy of the immobilisation of the chemotherapy drug doxorubicin on nanodiamond platforms as a potential cancer therapy. This...
This paper aims to demonstrate the efficacy of the immobilisation of the chemotherapy drug doxorubicin on nanodiamond platforms as a potential cancer therapy. This effective drug is experimentally fed into a human breast adenocarcinoma cell lines. Drug loading activity and cell viability are detected by spectrometer, microscopy, and MTT assay in this study at Biomedical Physics Research Unit, Department of Physics, Faculty of Science, King Mongkut's Institute of Technology Ladkrabang, Bangkok 10520, Thailand between 1 Oct 2018 and 10 Jun 2019. Experimental results show that in the basic environment (pH = 8.0), the nanodiamond carboxylic group cooperated with the doxorubicin amino group to form a stable and non-covalent bond on nanodiamond surfaces served as a simple physical adsorption. In an acidic environment suitable to targeting the cancer cells, the nanodiamond carboxylic group ionised so that doxorubicin is effectively released. Doxorubicin therefore affirmatively absorbed into the cytoplasm and later into the nucleus. The significant finding of the study is that IC-50 equivalent to 0.40 mg/mL and viable nanodiamond-doxorubicin is a good candidate material for drug delivery.
Topics: Adenocarcinoma; Adsorption; Animals; Antibiotics, Antineoplastic; Breast Neoplasms; Cell Nucleus; Cell Survival; Chlorocebus aethiops; Cytoplasm; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Humans; Hydrogen-Ion Concentration; Inhibitory Concentration 50; MCF-7 Cells; Nanodiamonds; Vero Cells
PubMed: 31608701
DOI: 10.1080/21691401.2019.1677681 -
Journal of Medical Imaging and... Jun 2024
Topics: Contrast Media; Doxorubicin; Humans; Chemoembolization, Therapeutic; Antibiotics, Antineoplastic; Drug Stability
PubMed: 38437190
DOI: 10.1111/1754-9485.13628 -
Current Drug Discovery Technologies 2021To utilize in silico-based approach for investigating the ability of PEGylated rapamycin as a competitive inhibitor to Galectin-3 for curing various diseases or that may...
AIMS
To utilize in silico-based approach for investigating the ability of PEGylated rapamycin as a competitive inhibitor to Galectin-3 for curing various diseases or that may provide an attractive strategy for treatment of a wide variety of tumors.
BACKGROUND
Galectin-3 (Gal-3) signaling protein is a unique member of lectin family present at the cell surface, intracellularly in both the nucleus and cytoplasm and extracellularly in the general circulation. Circulating Gal-3 is present in both normal and cancer cells. High levels of circulating Gal-3 have been proven to be associated with inflammation and fibrosis in several acute and chronic conditions, which include neurological degeneration, inflammatory and immune responses, autoimmune diseases, diabetes, heart failure, atherosclerosis, response to infection, wound healing, liver, lung, and kidney disease. Gal-3 is known to regulate many biological activities including cell adhesion, angiogenesis, growth, apoptosis, migration, and metastasis. Rapamycin has been examined alone or in combination with other drugs for treatment of various cancers in clinical studies. Although it has shown promising therapeutic effects, its clinical development was interrupted by poor aqueous solubility and limited preferential distribution. To overcome these limitations, RA has been chemically modified to hydrophilic analogues, such as everolimus (EV). However, all these approaches can only partially increase the solubility, but has little effect on the blood distribution and pharmacokinetics. Therefore, it is necessary to explore other RA conjugates to improve aqueous solubility and tissue distribution profile. Recently we reported that RP-MPEG inhibits the growth of various cancer cell lines by acting on mammalian target of RP (mTOR) receptor site and it can be used for gastric cancer.
OBJECTIVE
To construct various molecular weight RP-MPEG by replacing MPEG chain in 40-O-(2- hydroxyethyl) position of the EV and analyze their binding affinity to Gal-3.
METHODS
The chemical structures of various molecular weight RP-MPEG were built using ChemSketch software. The molecular docking study was performed to find the best probable structure of RP-MPEG for competitive inhibition of the CRD, based on the interaction score. For that purpose, the 3D structures of RP and EV were obtained from NCBI PubChem compound database, where the structural protein-co-crystallized ligand complex of Gal-3 (TD2, as a native ligand) was retrieved from RCSB Protein Data Bank. All structures of the selected compounds, served as molecules for molecular modeling, were optimized through MOE.2014 software before docking. Hydrogen atoms and partial charges were added to the protein. Protein minimization was performed in gas solvation with the side chains, keeping it rigid and the ligand flexible. The selected site was isolated and minimized, followed by protonating the protein. The 3D ligands were minimized using MMFF94x with cutoffs of 10 to 12 Å. The hydrogens and charges were fixed, and the RMS gradient was set to 0.001 kcal/mol. The docking results were analyzed to identify and assess the binding affinity of these compounds to CRD using drug discovery software.
RESULTS
Our results indicated that RP-MPEG with MW 1178.51 g/mol has a logP value of 3.79 and has possessed the strongest binding affinity toward CRD of Gal-3 with a docking score of -6.87. Compared with TD2, there were additional close contacts for RP-MPEG (MW 1178.51 g/mol), coming from three hydrogen bonds with Asp148, Arg162, and Arg144 which suggest that this ligand is a strong competitive inhibitor among the other molecules for Gal-3.
CONCLUSION
RP-MPEG with the MW 1178.51 g/mol could be a promising blocker for various biological action of Gal-3 includes profibrotic activity, modulation of immune responses and inflammatory responses to cancer that contributes to neoplastic transformation, angiogenesis and metastasis. Other: The 95% confidence intervals (CIs) of the binding affinity (according to their mean and standard errors) were estimated with 2.5 and 97.5 percentile as the lower and upper bounds.
Topics: Antibiotics, Antineoplastic; Blood Proteins; Galectins; Humans; Molecular Docking Simulation; Molecular Weight; Neoplasms; Polyethylene Glycols; Protein Binding; Sirolimus
PubMed: 31969105
DOI: 10.2174/1570163817666200122162042 -
Journal of Natural Products Sep 2020Four new tetrahydroanthracene derivatives (, -) and a known antibiotic, A-39183A (), were discovered from the marine-sponge-derived actinomycete HDN10255. Their...
Four new tetrahydroanthracene derivatives (, -) and a known antibiotic, A-39183A (), were discovered from the marine-sponge-derived actinomycete HDN10255. Their structures including absolute configurations were elucidated based upon MS and NMR spectroscopic data, ECD calculations, and biogenetic considerations. Compounds and showed considerable cytotoxicity with the best IC value of 1.8 μM against HeLa cells.
Topics: Animals; Antibiotics, Antineoplastic; Cell Line, Tumor; HeLa Cells; Humans; Isomerism; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Structure; Porifera; Streptomyces
PubMed: 32880456
DOI: 10.1021/acs.jnatprod.0c00805 -
Expert Opinion on Drug Delivery Mar 2024Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce... (Review)
Review
INTRODUCTION
Doxorubicin (DOX) emerges as a cornerstone in the arsenal of potent chemotherapeutic agents. Yet, the clinical deployment of DOX is tarnished by its proclivity to induce severe cardiotoxic effects, culminating in heart failure and other consequential morbidities. In response, a panoply of strategies has undergone rigorous exploration over recent decades, all aimed at attenuating DOX's cardiotoxic impact. The advent of encapsulating DOX within lipidic or polymeric nanocarriers has yielded a dual triumph, augmenting DOX's therapeutic efficacy while mitigating its deleterious side effects.
AREAS COVERED
Recent strides have spotlighted the emergence of DOX conjugates as particularly auspicious avenues for ameliorating DOX-induced cardiotoxicity. These conjugates entail the fusion of DOX through physical or chemical bonds with diminutive natural or synthetic moieties, polymers, biomolecules, and nanoparticles. This spectrum encompasses interventions that impinge upon DOX's cardiotoxic mechanism, modulate cellular uptake and localization, confer antioxidative properties, or refine cellular targeting.
EXPERT OPINION
The endorsement of DOX conjugates as a compelling stratagem to mitigate DOX-induced cardiotoxicity resounds from this exegesis, amplifying safety margins and the therapeutic profile of this venerated chemotherapeutic agent. Within this ambit, DOX conjugates stand as a beacon of promise in the perpetual pursuit of refining chemotherapy-induced cardiac compromise.
Topics: Doxorubicin; Cardiotoxicity; Humans; Animals; Antibiotics, Antineoplastic; Drug Carriers; Nanoparticles; Drug Delivery Systems; Polymers; Heart Failure; Lipids
PubMed: 38623735
DOI: 10.1080/17425247.2024.2343882