Current Topics in Medicinal Chemistry - Volume 18, Issue 25, 2018

Metabolomic analysis has made substantial contributions to the understanding of diverse pathological processes and has the potential to improve diagnosis and identify novel therapeutic targets. As early success in perinatal medicine, nutrition, chronic diseases, cancer and trauma demonstrates, metabolomics is approaching feasibility in terms of guiding improvement in population-level diagnosis and treatment. A key barrier to implementing metabolomics as a routine diagnostic tool is rapid sample extraction and data analysis along with the establishment of normal values for novel metabolic markers. This review covers key advancements in clinical metabolomics and applies a high throughput metabolomics method as a proof of principle to identify novel metabolites associated with remote ischemic preconditioning.

The development of xanthine oxidase and monoamine oxidase inhibitors led to important breakthroughs in the therapy of oxidative damage, hyperuricemia, gout, neurological, neuropsychiatric disorders and management of reperfusion injury. Drugs obtained from natural sources play an important role in the treatment of various pathological disorders and act as a lead compound for the discovery of new synthetic drug substances. In this review, various pharmacological effects produced by the inhibition of xanthine oxidase and monoamine oxidase through natural and synthetic flavonoids as well as anthraquinones are discussed in detail. Several methods have been designed for monitoring enzymatic activity and its inhibitor screening of bioactive natural and synthetic flavonoids and anthraquinones. In this review, all the in-vitro and other computational approaches are critically discussed which provided the clue about structure activity requirements for further precise modifications on the basic scaffold.

In the last few years, the fields of Medicinal Chemistry and especially the ones related to the so-called Personalized Medicine, have received a great attention. Significant investment and remarkable researches surround the matter; however, not all those promising advances are reaching patients as quickly as they should. The absence of an adequate regulatory framework could be of no help. The complete and/or massive sequencing of individual genomes faces many ethical-legal challenges. Some of them are access to Personalized Medicine; the treatment of a large volume of sensitive information and the use of tools produced by "big data" systems in clinical care or in predictive models. In addition, the legal protection of personal data related to health, the exercise of autonomy by patients, closely related to the regulation regarding clinical trials, are seriously involved. Our purpose of this work is to review the regulations of the European Union, in an attempt to contribute to a better understanding of the legal framework for the implementation and development of health systems based on Personalized Medicine.

Introduction: Renal Cell Carcinoma is a common type of renal cancer-causing deaths worldwide which is characterized by sustained angiogenesis. VEGF and its receptors play a major role in physiologic and pathologic angiogenesis, which is marked in tumour progression and metastasis development. Induction of VEGF genes occur due to hypoxic condition induced by tumour growth after a critical size in cancerous cell. Signal transduction networks originated by VEGFA/VEGFR2, (a notable ligand-receptor complex in the VEGF system) leads to major angiogenesis events ranging from endothelial cell proliferation, to new vessel formation, Furthermore, differential expression of VEGF-VEGFR mRNA also found in different types of RCC. Aim: The aim of present study is to inhibit the VEGFR2 protein by the action of certain inhibitors and then to search an efficient inhibitor. Materials and Methods: A total of 23 potential inhibitors were searched and used to target the protein using the concept of molecular docking. Among 23 inhibitors, CHEMBL346631 shows best affinity with the target protein and was used for high throughput virtual screening to find similar compounds. The compound obtained from virtual screeningSCHEMBL469307, shows much more better affinity with VEGFR2 than CHEMBL346631. Conclusion: Relative study for both the compounds showed a minor difference in relevant properties. The compound SCHEMBL469307 have a high potential to inhibit the VGFR2 protein and can be backed for future studies in Renal Cell Carcinoma.

Introduction: This increase in the prevalence of drug-resistant pathogens occurs at a time when the discovery and development of new antimicrobial agents occur slowly. In this context, the objective of this study was to investigate the antifungal activity of isoeugenol, a phenylpropanoid, by in vitro and in silico assays against Penicillium citrinum strains. Material and Method: For in silico analysis, the software PASS online, Molinspiration and Osíris were used. For the determination of Minimum Inhibitory Concentration (MIC) and Minimal Fungicide Concentration (MFC) of isoeugenol and voriconazole were carried out using the broth microdilution technique. PASS online has shown that isoeugenol has the opportunity to present antiseptic, antifungal, antibacterial, antimycobacterial activities. Molinspiration showed that the phytoconstituent has good potential for oral bioavailability. Conclusion: In the analysis with the Osiris program, it was demonstrated that isoeugenol has low irritant and tumorigenic risk. The MIC of isoeugenol varied between 256 and 32 μg/mL, MIC50 of 64 μg/mL and MIC90 was 128 μg/mL. The MFC50, MFC90 and MFC of the isoeugenol for P. citrinum species were 64, 256 and 518 μg/mL, respectively. After analysis, it was verified that the isoeugenol have bactericidal effect against the strains of P. citrinum. After these results, it is important to discover the mechanism of action involved in the antifungal action of the compound, as well as in vitro and in vivo toxicity tests.