Mini Reviews in Medicinal Chemistry - Volume 18, Issue 20, 2018

Since 1929, several researchers have conducted studies in relation to the nucleoside of adenosine (1) mainly distribution identifying, characterizing their biological importance and synthetic chemistry to which this type of molecule has been subjected to obtain multiple of its derivatives. The receptors that interact with adenosine and its derivatives, called purinergic receptors, are classified as A1, A2A, A2B and A3. In the presence of agonists and antagonists, these receptors are involved in various physiological processes and diseases. This review describes and compares some of the synthetic methods that have been developed over the last 30 years for obtaining some adenosine derivatives, classified according to substitution processes, complexation, mating and conjugation. Finally, we mention that although the concentrations of these nucleosides are low in normal tissues, they can increase rapidly in pathophysiological conditions such as hypoxia, ischemia, inflammation, trauma and cancer. In particular, the evaluation of adenosine derivatives as adjunctive therapy promises to have a significant impact on the treatment of certain cancers, although the transfer of these results to clinical practice requires a deeper understanding of how adenosine regulates the process of tumorigenesis.

Marine-derived fungi Trichoderma genus are serving as a valuable resource for structurally novel natural products encompassing a variety of chemical substances and diverse pharmacological applications. So far, about 78 metabolites have been structurally documented from the species of marine Trichoderma genus and a large proportion of these metabolites exhibited therapeutic properties with potential application in drug discovery. This mini-review focuses on the structures and bioactivities of these secondary metabolites from marine-derived Trichoderma species.

Thioflavone derivatives are the thio analogs of the core constituent of the natural product class of flavones. Based on the position and oxidation level of sulfur, they can be divided into three major categories: 4-thioflavones, 1-thioflavones and 1-thioflavones 1,1-dioxide. In recent years, great efforts have been made to develop an approach for the synthesis of thioflavones, especially 1- thioflavones with high functional group compatibility, high yields, low toxicity as well as proceeding under a mild condition, and a variety of synthetic protocols have been developed, the method of choice being dependent on the nature of substrates. As isosteric analogs of biologically active flavones, thioflavones also exhibit various pharmaceutical properties, such as antimicrobial, anticancer and neuroprotective activities. Replacement of the oxygen atom on flavone skeleton by a sulfur atom resulted in modified biological effects due in most part to the change of the structural properties. However, these varying effects depend on the substituents present and the test species. To provide a comprehensive vision of this class of compounds, this review primarily focuses on the structure, synthetic methods, biological properties as well as structure-activity relationships of thioflavones.

The review provides a summary of synthetic approaches to and medicinal applications of N-aryl-C-nitroazoles. This broad chemical family delivered numerous practical applications in the areas other than pharmaceuticals. This is most likely due to a common stigma associated with nitroheterocycles implying their inherent toxicity. Therefore, the research literature appears to be lacking in medicinal chemistry reports related to this class of compounds. However, despite this notion, the nitroheterocycles have enjoyed a marked renaissance in the last years, particularly, in antimicrobial area. Therefore, an attempt to summarize, within a single review article, the medicinal applications and methods of synthesis has been undertaken.

Background & Method: In this ongoing research, it is aimed to investigate the synthesis, structure identification and effects on urokinase-type plasminogen activators (uPA) and its receptor levels of 4-(3H-imidazo[4,5-b]pyridin-2-yl)-N-substituted benzamide and benzamidine derivatives. uPA levels obtained from 4b and 7d administration were similar to 5-FU (5-fluorouracil) for colorectal carcinoma cells (p<0.05). 4b and 7d significantly reduced uPAR (urokinase-type plasminogen activator receptor) levels on both cell lines (p<0.05). Conclusion: uPAR levels obtaining from 4b and 7d administration were similar to 5-FU for both cell lines colorectal (Colo205, CCL-222) and hepatocellular (HepG2, CCL-23) carcinoma cells (p<0.05).

Background & Method: A series of thirty-one new 1-phthalazinones was designed and synthesized based on the well-known VEGFR inhibitor vatalanib. The obtained phthalazinones were screened for their cytotoxic activity against DLD-1 and LoVo (colon), and Panc-1 and Paca-2 (pancreas) cancer cell lines using MTT assay. The tested compounds revealed exceptionally promising cytotoxic activity against LoVo cell lines with IC50 ranges 0.18-780 nM. Conclusion: Finally, these compounds were also found to be dual inhibitors of VEGFR-2 and EGFR in the in vitro enzyme assay with higher potency against the former (IC50 = 0.023-0.41 nM).