Current Topics in Medicinal Chemistry - Volume 18, Issue 14, 2018

Biomacromolecules structures and their interaction between different systems have been extensively studied in the last years. Nevertheless, in the medicinal context, it has not been studied deeply. For this reason, the interest to investigate the behavior of different biomacromolecules such us proteins, organelles, phospholipids, etc. with soft materials has opened new research lines. Computational and experimental methodologies have tried to answer different questions that have been difficult to solve, due to the complexity of the phenomenon, as an example, competition between biomacromolecules and soft materials for a specific organ. In this review, we would like to demonstrate how soft materials influence the biomacromolecules structures and how to change their response, biodistribution and also biocompatibility for future applications.

Bacterial resistance is a growing problem worldwide and is estimated that deaths by infectious diseases associated with resistant pathogens will generate 10 million deaths per year in 2050. This problem becomes more serious due to the low level of research and development of new drugs, which has fallen drastically in the last 40 years. For example, in the last decade of a total of 293 new drugs approved by the FDA, only 9 corresponded to antimicrobial drugs and none constituted a new structural class. The majority of the molecules in the clinical phase II or III, coming from modifications of drugs in clinical use, this strategy makes easier the bacterial susceptibility to generate resistance through the mechanisms expressed for their drug predecessors. Under this scenario, it is urgent to generate the most novel strategies for the development of antibacterial compounds with new targets or mechanism of action, without a structural relationship with the antibiotic drugs predecessors. Under this look, the present review addresses the development of the latest antibacterial drugs in clinical phases II and III, analyzing the design strategies by which these new molecules were obtained and the structure-activity relationship of these new families of antibiotics, in order to define the state of the vanguard antibacterial drugs in the post-antibiotic era.

Machine Learning (ML) models are very useful to predict physicochemical properties of small organic molecules, proteins, proteomes, and complex systems. These methods may be useful to reduce the cost of research in terms of materials resources, time, and laboratory animal sacrifice. Recently different authors have reported Perturbation Theory (PT) methods combined with ML to obtain PTML (PT + ML) models. They have applied PTML models to the study of different biological systems and in technology as well. Here, we present one state-of- the-art review about the different applications of PTML models in Organic Synthesis, Medicinal Chemistry, Protein Research, and Technology. In this work, we also embrace an overview of regulatory issues for acceptance and validation of both: the Cheminformatics models, and the characterization of new Biomaterials. This is a main question in order to make scientific result self for humans and environment.

Tissue engineering provides solutions that require medicine to restore damaged tissues or even complete organs. This discipline combines biologically active scaffolds, cells and molecules; being the addition of nanoparticles into the scaffolds, one of the techniques that is attracting more interest these days. In this work, Hydroxyapatite Nanorods (HA) were added to the network of Gelatin hydrogel (GE), and the particular properties resulting from their interaction were studied. Specifically, viscoelastic properties were characterized as a function of gel and nanoparticle concentration, varying ratios and temperatures. Oscillatory Time Sweeps (OTS) provided the necessary information about how the timeresolved material property/structure alteration. A wide variety of Continuous Flow Tests and Frequency Sweeps were used to describe the mechanical properties of the material, proving that the presence of nanoparticles led to a reinforcement of the gel network, mechanical stiffness and strength. The thixotropic nature of the gels was also evaluated and the most common theoretical models were described and commented. The attributes inferred from the data, showed a material that can allow the natural growth of bone tissue whilst withstanding properly the mechanical efforts; resulting in a material with an outstanding suitability to be used in regenerative medicine.

The use of colloidal particles as drug delivery carriers holds a great promise in terms of improvement of traditional treatment and diagnosis of human diseases. Nano- and microsized particles of a different composition including organic and inorganic materials can be fabricated with a great control over size, shape and surface properties. Nevertheless, only some few formulations have surpassed the benchtop and reached the bedside. The principal obstacle of colloidal drug delivery systems is their poor accumulation in target tissues, organs and cells, mainly by efficient sequestration and elimination by the mononuclear phagocytic system. Recent evidence suggests that, besides size, the surface character of colloidal systems is the most determinant design parameter that may ultimately guarantee successful biological performance. To approach these issues, materials designers and engineers can make use of multiple strategies and tools to finely modulate the particles' surface towards highly efficient and biocompatible materials. In this article, we provide an overview of the most relevant colloidal drug delivery systems, a summary of the available literature regarding the effects of surface charge, hydrophobicity and softness on biological response, and finally, we review the key points of surface modification strategies with organic, inorganic and biological materials.

Collagen, the most abundant component in mammalian tissues, has a crucial impact at skin level. Both promotion and maintenance of cross-linked collagen at the skin are critical to sustain the functionality and appearance of that tissue. Lysyl oxidases, also known as LOX enzymes, are the major collagen cross-linking enzymes that play a pivotal role in homeostasis. This minireview summarizes evidence that describes an amino oxidase-like activity, which could be attributed to polyphenols, or where polyphenols could be required. We also discuss some available collagen formulations and the scientific evidence that describes the impact on dermal extracellular matrix. In addition, information about encapsulation strategies to carry polyphenols, and some examples are also provided.

In this study, allyl-isothiocyanate (AITC)-loaded Polylactic-Co-Glycolic Acid (PLGA) Nanoparticles (NPs) were prepared for targeting epithelial squamous carcinoma cells using a specific antibody targeting the Epidermal Growth Factor (EGF) receptor overexpressed on the cell membranes. AITC-loaded PLGA NPs showed more effective anticancer properties compared with free AITC, and their cytotoxicity was even more pronounced when the anti-EGFR antibody was covalently attached to the NPs surface. This targeting ability was additionally tested by co-culturing cervical HeLa cells, with very few EGFR on the membranes, and epithelial squamous carcinoma A431 cells, which largely overexpressed EFGR, being observed the specific localization of the antibody-functionalized AITC-loaded PLGA NPs solely in the latter types of cells, whereas non-functionalized NPs were distributed randomly in both cell types in much lesser extents. Thus, our findings support the development of drug delivery strategies that enhances the delivery of anti-cancer natural compounds to tumor tissue, in this case, by targeting specific tumor cell receptors with cell-specific ligands followed by tumor sensitization.

Recently, Pectin (PEC) and Aloe-Gel (AG) have received great attention for their use in the encapsulation of hydrophobic bioactive compounds such as Carvacrol (CAR). The aim of this study is to assess the physical, chemical and biological properties of a novel PEC/AG film and evaluate its capability to entrap CAR into microencapsulates. For this purpose, the casting method was used to prepare the PEC/AG membranes (70:30 % w/w). The CAR-loaded PEC/AG film was prepared adding different proportions of CAR (0.25%, 0.50% and 1.00% v/v) to the mixture of PEC/AG, previously emulsified with tween 80 (1.0%). The optical properties, Water Vapor Permeability (WVP), ATR-FTIR spectroscopy, microstructure, antibacterial activity and size of microcapsules were evaluated. The PEC/AG membranes loaded with CAR showed yellowish appearance and they were transparent to the UV electromagnetic radiation (190, 200 and 280 nm). The film prepared with the lowest amount of CAR (PC/AG-CAR-0.25%) showed the highest values of WVP (66.2%) and, according to SEM micrograph, the largest microcapsules (≈1005± 39 μm3). The FTIR analysis showed the characteristic absorption peaks located at 1015 cm-1 to 1030 cm-1 and a small shoulder to 990 cm-1 of benzene ring 1:2:4 substituted that suggested the presence of CAR-loaded in the PC/AG film. On the other hand, E. coli O157:H7 showed the highest sensitivity to the PEC/AG-CAR-1.00% film, while S. aureus was not sensitive.