The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.
The aim of this investigation is to identify, by in silico and in vitro methods, the molecular determinants, e.g., solubility in an aqueous medium and lipophilic properties, which have an effect on the bioavailability of five selected fluoroquinolones. These properties were estimated by analysis of the electrostatic potential pattern and values of free energy of solvation as well as the partition coefficients of the studied compounds. The study is based on theoretical quantum-chemical methods and a simple experimental shake-flask technique with two immiscible phases, n-octanol and phosphate buffer. The solvation free energy values of compounds in both environments appeared to be negative. The wide range of electrostatic potential from negative to positive demonstrates the presence of dipole–dipole intermolecular interactions, while the high electron density at various sites indicates the possibility of hydrogen bond formation with solvent molecules. High partition coefficient values, obtained by summing the atomic contributions, did not take various correction factors into account and therefore were not accurate. Theoretical partition coefficient values based on more accurate algorithms, which included these correction factors (fragmental methods), yielded more accurate values. Theoretical methods are useful tools for predicting the bioavailability of fluoroquinolones.
Fullerene molecules are created entirely of carbon and form orbicular or ellipsoidal cage shape similar to a hollow tube. The derivatives of fullerenes are classified into the following categories according to their functionalization: endohedral fullerenes with active molecules residing inside the carbon cage, exohedral with wide variety of both inorganic and organic groups existing outside and connected to the fullerenes' exterior and heterofullerenes when one or more carbon atoms that form the fullerene carbon cage are replaced by a non-carbon atom, i.e. a heteroatom. Fullerene C 240 belongs to the family of giant fullerenes and is characterized by a greater stability than that of the well-known fullerene C 60 . This has been proved by observing an increased formation heat that accompanied the decreasing of the carbon cage size.In order to determine the fullerene C 240 ability to transport the steroid hormones: estradiol, progesterone, androsterone and their basic structures: estrone, androstane and pregnane, the following parameters, inter alia, have been calculated: energies of stabilization, interaction and deformation of each endohedral complex. The calculations for all chosen structures were carried out with the use of the molecular modeling technique. Based on all available studies, it can be stated that fullerene C 240 could be a solution for problems faced by medicine and pharmacy.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.1869v1 | CC-BY 4.0 Open Access |
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