Mini Reviews in Medicinal Chemistry - Volume 18, Issue 5, 2018

The applications of optimal molecular descriptors as a tool to predict endpoints related to medicinal chemistry are listed. The general scheme of building up of the optimal descriptors is represented in detail. Simplified molecular input-line entry system (SMILES) is being used to represent the molecular architecture. The optimal descriptor is the sum of correlation weights of molecular fragments extracted from SMILES. The numerical data on the correlation weights are calculated by the Monte Carlo method. The data should provide maximal correlation coefficient between experimental values of endpoint and corresponding values of the optimal descriptor. The scheme contains two phases: (i) selection of reliable parameters of the Monte Carlo optimization; and (ii) building up a model. The mechanistic interpretation for models based on the optimal descriptors is suggested. The interpretation is calculated on results of several runs of the Monte Carlo optimization. The domain of applicability for these models is defined according to the prevalence of molecular fragments in the training and calibration sets.

Among the family of nitrogen-containing heterocycles, quinoxalinone (or quinoxalin-2-one) core, characterized by pyrazin-2(1H)-one fused to benzene ring at two adjacent carbon atoms, has been frequently found in a variety of pharmacologically active compounds with biological or pharmaceutical applications. It was gratifying that a larger part of these bioactive quinoxalinone-based derivatives has entered various clinical trials, which in turn hastens the synthetic versatility and also initiates various derivatization of quinoxalinone scaffold. In this review, we highlighted the newly emerged quinoxalinone- based derivatives or analogues, with the emphasis of their biological applications and structure-activity analysis covering literatures in recent years.

Conventional dressings are cost-effective and highly absorbent, but not effectual enough to promote hemostasis, adherence and in holding a moist wound bed. Thanks to the developments in the field of nanotechnology and bioengineering, one of the promising current trends is to move progress of innovative wound dressings, merging the application of traditional healing agents and modern products/ practices, such as hydrocolloids, hydrogels, films and nanofibers. This review surveys on potentials of electrospun nanofibrous mats for wound dressing applications. Furthermore, loading of bioactive molecules and therapeutic agents into the nanofibrous mats especially natural compounds with the aim of fabrication novel bioactive electrospun nanofibrous mats for skin substitutes and wound dressings are discussed. Systematic literature search was conducted to review all recent progress toward the potential of natural substances incorporated with electrospun nanofibrous scaffolds for wound dressing applications. The electrospun nanofibers webs can provide the essential parameters require for wound dressing to heal wounds including absorptivity, oxygen permeability, and non-adherence to the healing tissue, barrier to bacteria, bioactivity and occlusivity. The modern wound dressings materials made of electrospun nanofibers contain various traditional healing agents such as plant derived compounds could be beneficial to the healing of wounds. Natural substances have been used in skin wound care for many years because of their therapeutic properties, including antimicrobial, antioxidant, anti-inflammatory and mitogenic activities. A screening of natural substances with plant or animal sources having high wound healer activities and cooperating with electrospun nanofiber are an important step toward producing innovative bioactive wound dressings.

Glucocorticoids are steroid hormones that exert most of their effects through their binding to the glucocorticoid receptor (GR), a ligand regulated transcription factor. Although glucocorticoids are widely used in the clinic, their usage in chronic therapies provokes severe adverse reactions. In the quest for safer glucocorticoids a dissociated model was established that proposes a disconnection between GR activated pathways responsible of desired pharmacological effects and pathways involved in adverse GR reactions. Under this model, a myriad of steroidal and non-steroidal compounds has been characterized, with most of them still producing side effects. X-ray crystallographic studies followed by molecular dynamics analysis led research to insights on the receptor Ligand Binding Domain (LBD), which undergoes specific ligand dependent conformational changes that influence receptor activities. In this sense, the flexibility of the ligand structure would contribute to the final GR outcome. Here, we review different data of 21-hydroxy-6,19-epoxyprogesterone (21OH-6,19OP), a rigid steroid with potential pharmaceutical interest due to its anti-inflammatory and immunosuppressive activities, lacking several GR adverse reactions. The rigid structure endows this compound with an enhanced selectivity towards GR. Molecular characterization of the GR/21OH-6,19OP complex revealed specific intermediate conformations adopted by the receptor that would explain the influence on GR dimerization and the recruitment of a specific set of GR transcription modulators. We summarize recent data that will contribute to understand the complexity of glucocorticoid response.

Dendrimers are hyper branched macro molecules with well-defined structure and high degree of functionality on the surface. The dendrimer architecture allows control over properties such as shape, size, density, polarity, reactivity, solubility etc. These special features can be exploited to design molecules having desired properties used for biomedical applications. Recent advancements in correlation between structure and biodegradability and in vivo performance are opening up new avenues for these molecules; particularly, in biological applications like drug delivery. The unique structure of dendrimers provides enough attachment sites for drugs. Further, it is possible to tune the molecules in such a way so that the drug molecules are encapsulated outside the target area and are released only in the local environment of targets. This review presents some general aspects of dendrimers and how their properties are exploited for drug delivery applications.

Narcolepsy is an incurable neurological disorder when the brain is not able to regulate a sleep and wakefulness cycle correctly. The affected person suddenly falls asleep during the day or he/she suffers from excessive day sleepiness. In addition, people may also suffer from cataplexy, hypnagogic hallucinations, sleep paralysis, and disturbed nighttime sleep. The purpose of this review study is to provide the latest information on both clinical and socioeconomic issues in the field of narcolepsy treatment and emphasize its benefits and limitations. The methodological approaches include a method of literature review of available sources exploring the issue of narcolepsy, both from a global and specific perspective point of view. On the basis of evaluation of these literature sources, the researched issue is examined. The main benefits (e.g., new drugs are being tested or non-invasive cognitive behavioral therapies are being applied) and limitations (e.g., late diagnosis of the disease or lifelong and costly treatment) of the treatment of narcolepsy are highlighted. The findings call for more research in the field of the development of novel drugs reflecting understanding of the neurological basis of narcolepsy and early diagnosis in order to eliminate the symptoms of narcolepsy and prevent the development of this disease.