Mini Reviews in Medicinal Chemistry - Volume 20, Issue 4, 2020

The current trend of increment in the frequency of antifungal resistance has brought research into an era where new antifungal compounds with novel mechanisms of action are required. Natural antimicrobial peptides, which are ubiquitous components of innate immunity, represent their candidature for novel antifungal peptides. Various antifungal peptides have been isolated from different species ranging from small marine organisms to insects and from various other living species. Based on these peptides, various mimetics of antifungal peptides have also been synthesized using non-natural amino acids. Utilization of these antifungal peptides is somehow limited due to their toxic and unstable nature. This review discusses recent updates and future directions of antifungal peptides, for taking them to the shelf from the bench.

Background: In the recent years, many novel Disease-Modifying Drugs (DMD) have been introduced to the market in the treatment of multiple sclerosis. Objectives: To provide the reader with an up to date, compact review on the pharmacokinetic properties, mechanism of action, and clinical attributes of one of the most recently approved drugs in the therapy of multiple sclerosis, cladribine. Conclusion: Cladribine tablets proved to be a highly efficient treatment choice for Relapsing- Remitting Multiple Sclerosis (RRMS), especially for patients with high disease activity. It is the first DMD for MS with a complex mechanism of action, by inhibiting the adenosine-deaminase enzyme it increases the intracellular levels of deoxyadenosine triphosphate, which with relative selectivity depletes both T- and B-cells lines simultaneously. However long term follow-up safety and effectiveness data are still missing, and clear treatment protocols are lacking beyond the first two treatment years cladribine should prove to be a valuable addition to the therapeutic palette of RRMS, and potentially for Clinically Isolated Syndrome (CIS) as well.

Flavonoids are an important class of phytopharmaceuticals in plants. Naringin (naringenin- 7-O-rhamnoglucoside) is a flavanone glycoside isolated from folk herbal medicine Exocarpium Citri grandis (called Huajuhong in Chinese). Massive experimental works have been performed on naringin describing its phytochemical, pharmacokinetic, and bioactive properties. Naringin was found to possess multiple pharmacological activities in relieving inflammation, diabetes, neurodegeneration, cardiovascular disorders, and metabolic syndrome. Recently, it has been approved as a potential antitussive and expectorant for clinical trials. However, the pharmacokinetic aspects of naringin and its therapeutic potentials in respiratory diseases have not been comprehensively reviewed. The present review provides highlights of naringin with respect to its absorption, distribution, metabolism, excretion and its therapeutic effects on cough, phlegm, and pulmonary inflammation. This review would be helpful for the interpretation of pharmacokinetics and pharmacodynamics of naringin in clinical trials.

The concept of nanoscale materials and their applications in industrial technologies, consumer goods, as well as in novel medical therapies has rapidly escalated in the last several years. Consequently, there is a critical need to understand the mechanisms that drive nanomaterials biocompatibility or toxicity to human cells and tissues. The ability of nanomaterials to initiate cellular pathways resulting in oxidative stress has emerged as a leading hypothesis in nanotoxicology. Nevertheless, there are a few examples revealing another face of nanomaterials - they can alleviate oxidative stress via decreasing the level of reactive oxygen species. The fundamental structural and physicochemical properties of carbonaceous nanomaterials that govern these anti-oxidative effects are discussed in this article. The signaling pathways influenced by these unique nanomaterials, as well as examples of their applications in the biomedical field, e.g. cell culture, cell-based therapies or drug delivery, are presented. We anticipate this emerging knowledge of intrinsic anti-oxidative properties of carbon nanomaterials to facilitate the use of tailored nanoparticles in vivo.

2,4-Thiazolidinedione (2,4-TZD) is a versatile pharmacophore, a privileged scaffold, and a remarkable sulphur-containing heterocyclic compound with diverse pharmacological activities. The multifarious biological activities, due to different mechanisms of action, low cost, and easy availability of 2,4-TZD impressed medicinal chemists to integrate this moiety to develop various lead compounds with diverse therapeutic actions. This resulted in the swift development in the last decade for generating different new potential molecules bearing 2,4-TZD. In this review, the authors attempt to shape and present the latest investigations (2012 onwards) going on in generating promising 2,4-TZD containing lead compounds. The data has been collected and analyzed to develop the structure-activity relationship (SAR). The SAR and active pharmacophores of various leads accountable for antidiabetic, anticancer, antimicrobial, and antioxidant activities have also been illustrated. This review also highlighted some of the important chemical synthetic routes for the preparation of various 2,4-TZD derivatives. This review will definitely serve as a useful source of structural information to medicinal chemists and may be utilized for the strategic design of potent 2,4-TZD derivatives in the future.

Biopolyesters represent a large family that can be obtained by polymerization of variable bio-derived hydroxyalkanoic acids. The monomer composition, molecular weight of the biopolyesters can affect the properties and applications of the polyesters. The majority of biopolyesters can either be biosynthesized from natural biofeedstocks or semi-synthesized (biopreparation of monomers followed by the chemical polymerization of the monomers). With the fast development of synthetic biology and biosynthesis techniques, the biosynthesis of unnatural biopolyesters (like lactate containing and aromatic biopolyesters) with improved performance and function has been a tendency. The presence of novel preparation methods, novel monomer composition has also significantly affected the properties, functions and applications of the biopolyesters. Due to the properties of biodegradability and biocompatibility, biopolyesters have great potential in biomedical applications (as implanting or covering biomaterials, drug carriers). Moreover, biopolyesters can be fused with other functional ingredients to achieve novel applications or improved functions. This study summarizes and compares the updated preparation methods of representative biopolyesters, also introduces the current status and future trends of their applications in biomedical fields.