Current Medicinal Chemistry - Volume 28, Issue 40, 2021

Background: Natural biopolymers have drawn extensive attention because of their great biocompatibility, biodegradability, renewability, and the availability of various reactive functional groups for modifying and introducing novel components. In the last few years, numerous natural biopolymer composites have been exploited to improve their physical and chemical properties and add new functionalities. Methods: Herein, we summarize the current progress in three common classes of natural biopolymer-based composites, including alginate, chitosan, and gelatin. Results: The morphology characteristics, preparation methods, and unique functionalities of these biopolymer composites are also analyzed and discussed. Conclusion: Finally, the article offers an overview of recent progress in the main biomedical applications such as tissue engineering, wound-healing, and drug delivery, which inspires further progress in biopolymer composites with tailored mechanical property and stable characteristics for pharmaceutical and biomedical applications.

Phage display is a powerful high-throughput screening technology that presents a large and diverse selection of functional peptides, proteins, or antibody fragments on phage capsid surfaces for affinity determination towards a target of interest. Due to its advantages of a large screening capacity, mass production through fermentation, and straightforward execution, phage display has been widely used in bioengineering and biomedicine, especially for diagnostics and therapeutics. With the advent of next-generation sequencing and microfluidics technologies, phage display has become an even more powerful and popular tool for drug discovery and development. Here, we briefly review phage display technology and its application to drug discovery, including the discovery and development of peptide-based drugs and monoclonal antibodies. Combined with the emerging proteolysis targeting chimeras (PROTAC), we also discuss the advantages and future directions, aiming to facilitate drug discovery and development.

Background: Recently, there has been increasing interest in nanomaterials processed using renewable and sustainable resources. Nanocellulose-based materials are of paramount value in the applications of biomedicine owing to their tailorable surface modification, favorable optical transparency, good hydrophilicity, excellent biocompatibility, and outstanding mechanical properties. Objective: In the review, the recent advancements of nanocellulose, including cellulose nanofibers (CNFs), cellulose nanocrystals (CNCs), and bacterial cellulose (BC), are summarized, which are promising for biomedical applications. Results: By discussing different forms (one-dimensional (1D), two-dimensional (2D), and three-dimensional (3D)), the superiority of the nanocellulose-based materials with different constructed structures will be clarified for various biomedical applications, such as biosensing, drug delivery, wound dressing, and tissue engineering. Conclusion: The challenges and prospects for the future development of nanocellulose- based materials in biomedical applications are also discussed at the end of the review.

Background: Cellulose, having huge reserves of natural polymers, has been widely applied in pharmaceutical and biomedicine fields due to its good biocompatibility, biodegradability, non-toxicity and excellent mechanical properties. At present, water- resistant metal-based and petroleum-based materials applied in the medical field have obvious problems of poor biocompatibility and high cost. Therefore, water-resistant cellulose- based materials with good biocompatibility and low price have become an attractive alternative. This review aims to summarize the preparation of water-resistant cellulose- based materials and their potential application in pharmaceutical and biomedical in recent years. Methods: Common hydrophobic treatments of cellulose fibers or paper were overviewed. The preparation, properties and applications of water-resistant cellulose- based materials in the pharmaceutical and biomedical fields were summarized. Results: Common hydrophobic treatments of cellulose fibers or paper were divided into chemical modification (graft polymerization, crosslinking, solution casting or dip-coating), physico-chemical surface modifications (plasma treatments, surface patterning, electrostatic spraying and electrowetting) and physical processing (electrostatic spinning, SAS process and 3D EHD printing). These hydrophobically processed cellulose fibers or paper could be prepared into various water-resistant cellulose-based materials and applied in pharmaceutical excipients, drug-loaded amphiphilic micelles, drug-loaded composite fibers, hydrophobic biocomposite film/coatings and paper-based detectors. They presented excellent water resistance and biocompatibility, low cytotoxicity and high drug loading ability, and stable drug release rate, etc., which could be used for water-insoluble drugs carriers, wound dressings, and medical testing equipment. Conclusion: Currently, water-resistant cellulose-based materials were mainly applied in water-insoluble drugs delivery carriers, wound dressing and medical diagnosis and presented great application prospects. However, the contradiction between hydrophobicity and mechanical properties of these reported water-resistant cellulose-based materials limited their wider application in biomedicine such as tissue engineering. In the future, attention will be focused on the higher hydrophobicity of water-resistant cellulose-based materials with excellent mechanical properties. In addition, clinical medical research of water-resistant cellulose-based materials should be strengthened.

Background: Bacterial cellulose (BC) and its derivatives are a rich source of renewable natural ingredients, which are of great significance for biomedical and medical applications but have not yet been fully exploited. BC is a high-purity, biocompatible, and versatile biomaterial that can be used alone or in combination with other ingredients such as polymers and nanoparticles to provide different structural organization and function. This review briefly introduces the research status of BC hydrogels, focusing on the preparation of BC-based composite hydrogels and their applications in the field of biomedicine, particularly the wound dressings, tissue engineering scaffolds, and drug delivery. Methods: By reviewing the most recent literature on this subject, we summarized recent advances in the preparation of BC-based composite hydrogels and their advances in biomedical applications, including wound dressings, tissue engineering, and drug delivery. Results: BC composite hydrogels have broadened the field of application of BC and developed a variety of BC-based biomaterials with excellent properties. BC-based hydrogels have good biocompatibility and broad application prospects in the biomedical field. Conclusion: BC-based composite hydrogels with the advantages of 3D structure, nontoxicity, high purity, and good biocompatibility, have great prospects in the development of sustainable and multifunctional biomaterials for biomedical applications.

The recent pandemic due to SARS-CoV-2, the last isolated human betacoronavirus, has revolutionized modern knowledge of the pathogenesis of viral pneumonia. The lack of specific antiviral drugs and the need to develop adequate research for new antiviral drugs capable of treating this new form of the disease undertook three different research paths quickly. The first one is aimed to test antiviral molecules already present in therapeutic use, with a mechanism of action directed towards viral proteins functional to replication or adsorption; the second one, it is the repositioning of molecules with known pharmacological activity for which various chemistry studies have been prepared in an attempt to find new and specific viral targets; the third, it is the search for molecules of natural origin for which to demonstrate a specific anti-coronavirus activity. Many databases of natural and synthetic substances have been used for the identification of potent inhibitors of various viral targets. The field of computer-aided drug design seems to be promising and useful for the identification of SARS-CoV-2 inhibitors; hence, different structure- and ligand- based computational approaches have been used for their identification. This review analyzes in-depth and critically the most recent publications in the field of applied computational chemistry to find out molecules of natural origin with potent antiviral activity. Furthermore, a critical and functional selection of some molecules with the best hypothetical anti-SARS-CoV-2 activity is made for further studies by biological tests.

Progressive globalization of our society brings not only worldwide integration, it also increases and promotes our exposure to new viral pathogens with evident impacts on our global health. Especially with the emergence of SARS-CoV-2, our biomedical research infrastructure has never been more compelled to rapidly develop antiviral regimens that demonstrate improved efficacy against these pathogens. Here, we showcase 3 poignant antivirals against the lucrative target, RNA-dependent RNA polymerase (RdRP) of RNA viruses – a timely and relevant topic given the present efforts against COVID-19. While effective drug designs against RdRP are important, their benefit and potential as a standard of care truly relies on them standing out in well-designed clinical trials.

Prostate cancer (PCa) carries a growing burden on society. Lack of curative treatment and poor prognosis among patients with advanced PCa imply an urgent need for novel and improved drug identification. This is hampered by the disease's high molecular heterogeneity and complex molecular pathophysiology, resulting in drugs being efficient in a few patients and cancer developing resistance to treatment. De novo drug discovery has proven to be complex and challenging. Along with technological advancements (mainly linked to –omics approaches) that allow for comprehensive characterization of the molecular changes underlying disease, and considering respective developments in bioinformatics, computational drug repurposing has emerged as a promising approach to shorten the way from discovery to clinical application and address the disease molecular complexity. With this article, we aimed at reviewing recent studies in which drugs/ compounds for PCa were defined through the investigation of molecular profiling (-omics) data and the application of drug repurposing strategies. A brief overview of the technical requirements and associated challenges with the latter are also provided. For that purpose, a literature search was conducted using the PubMed database. Numerous drugs/ compounds have been proposed as potential PCa therapeutics, mostly based on the investigation of genomics and transcriptomics data. In most cases, further assessment in disease models is required. Since ultimately proteins are targeted by drugs, expanding on the use of proteomics profiling data (alone or in combination with other –omics) is expected to advance further defining new/repurposed drugs for PCa.

This mini-review focuses on the investigation of novel nitrogen-containing steroid derivatives that are potentially applicable for prostate cancer treatment. It covers the literature of the last decade, highlighting the structure of new steroid compounds that exhibit significant activity in prostate cancer cells and possess pharmacological potency. New derivatives of known anti-prostate cancer agents: abiraterone and galeterone, new derivatives of androstane and pregnane modified with nitrogen-containing heterocycles, and some related steroid-derived compounds are discussed in the review.

Background: Cell heterogeneity exists among different tissues, even in the same type of cells. Cell heterogeneity leads to a difference in cell size, functions, biological activity, and for cancer cells it causes different drug responses and resistance. Meanwhile, microfluidics is a promising tool for single-cell research to reveal cell heterogeneity. Methods: Through literature research conducted over the past ten years on microfluidics, we summarize and introduce the application of microfluidics in single-cell separation and manipulation, featuring techniques, such as acoustic manipulation, optical manipulation, single-cell trapping, and patterning, as well as single-cell omics including singlecell genomics, single-cell transcriptomics, single-cell proteome, single-cell metabolome, and drug development. Results: Microfluidics is a flexible, precise tool, and it is easy to integrate with different functions. Firstly, it can be used as an important tool to separate rare but important cells according to the cell`s biological or physical properties. Secondly, microfluidics can provide the possibility of single-cell omics. Thirdly, microfluidics can be used in drug development, specifically in drug delivery and drug combination. Meanwhile, droplet microfluidics has gradually become the most powerful tool to encapsulate single-cells with other reagents for DNA, RNA, or protein analysis. Conclusion: Microfluidics is a robust platform technology that is able to accomplish rare cell separation, efficient single-cell omics analysis and provide a platform for drug development and drug delivery.