Mini Reviews in Medicinal Chemistry - Volume 18, Issue 13, 2018

Recently, the marine-derived Aspergillus present as producers of a large number of structurally novel secondary metabolites. Some of these metabolites have shown antitumor, antimicrobial, anti-inflammatory, antioxidant and enzymatic activities, and may be promising resources for new therapeutic drugs. This review sums up 232 new bioactive metabolites from the marine-derived Aspergillus with classification through their biological activities and chemical structures in 2006-2016. Besides, structure-activity relationships of some compounds are explored.

Mushrooms have been used as traditional medicine from last few decades. Mushrooms as higher Basidiomycetes contain secondary metabolites in fruit bodies, cultured mycelium, and cultured broth. Medicinal mushrooms possess medicinal properties such as anti-tumor, immunomodulating, antioxidant, cardiovascular, anti-hypercholesterolemic, anti-viral, anti-bacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and anti-diabetic effects. Phase-I, II, and III clinical trials were studied on various biologically active compounds isolated from medicinal mushrooms and are used adequately to treat various diseases including cancer. The present review focuses on various edible, medicinal and poisonous species of mushrooms belong to genera; Auricularia, Cantherallus, Ganoderma, Pleurotus, Lentinus, Trametes (Coriolus), Tremella and Amanita along with their chemical composition, biologically active compounds isolated and their pharmacological potential.

Malaria is one of the major infectious diseases and foremost cause of mortality and morbidity in many subtropical and tropical regions. In the last years, the situation has become worst in many ways, due to increase in the parasites resistance to various available antimalarial agents. Furthermore, malaria's control is beginning to be more sophisticated by the parallel spread of mosquito vector's resistance to the available insecticides. Recently, there is a wide consensus to seek for target specific, safe, affordable, and effective new antimalarial agents, which can compete with synthetic ones. Endophytic fungi are of a growing interest as prominent sources of structurally unique bioactive natural products. The bio-metabolites isolated from endophytic fungi, possessing antimalarial potential may compose the base for the synthesis of novel drugs that might be utilized to withstand malaria and its resistance. For getting information on the various studies, PubMed, Google Scholar, ScienceDirect, SpringerLink, Scopus, and Wiley search was done using keywords (malaria, endophytic fungi, and antimalarial activity). The present review covers the literature published from 1996 to 2017 and highlights the metabolites for which antimalarial activities have been reported. Overall, 135 fungal metabolites and 72 references are cited. In addition, their structure, chemical class, fungal source, host, and activity have been presented. This review shows the significance of endophytic fungi as a wealthy pool of antimalarial agents.

Locally advanced, muscle-invasive urothelial carcinoma of the bladder (MIBC) may be definitively treated with either radiotherapy or radical cystectomy (RC) with urinary diversion. Neoadjuvant chemotherapy (NAC) is typically administered prior to treatment with either modality. Receiving NAC prior to RC might confer a survival advantage compared to undergoing RC alone. However, its usefulness has been questioned due to concerns about over treatment and toxicity. Having the ability to predict whether individual patients would benefit from or be harmed by NAC would be an important tool in precision medicine. Unfortunately, to date no prognostic or predictive molecular markers have been validated for this purpose. In this manuscript, we review the current state of molecular markers in MIBC treatment and outline how recent advances in whole-genome sequencing may soon improve the selection of precisely targeted therapeutics for the benefit of individual patients.

Bladder cancer is the most prevalent malignancy of the urinary tract and is associated with significant morbidity and mortality. Preventative efforts to reduce the medical and financial burdens of bladder cancer are highly desirable. However, the utilization of natural and pharmaceutical products for the prevention and treatment of bladder cancer remains largely controversial. Herein, we review the current body of evidence surrounding a number of natural dietary substances and their roles in chemoprevention of bladder cancer. Possible chemopreventative properties of several pharmaceutical agents are also reviewed. Overall, the current body of evidence is insufficient to establish a clear link between these proposed chemopreventive agents and risk of bladder cancer.

Sirtuins are a family of NAD+-dependent deacetylases (class III histone deacetylases). Seven mammalian sirtuins, SIRT1-7, are identified, as the functions and locations differ greatly. SIRT1 and SIRT2 locate in nucleus and cytoplasm, while SIRT3-5 in mitochondria. Sirtuins are not only involved in many important biological processes such as apoptosis, cellular senescence, endocrine signaling, glucose homeostasis, aging, and longevity, it can also control circadian clocks and mitochondrial biogenesis. Small molecules that can modulate the sirtuins activity have been shown to have potentials for treating many human diseases such as type II diabetes, cancer, rheumatoid arthritis, cardiovascular and other age-relating diseases. Some polyphenolic natural products such as Resveratrol, Fisetin, and Quercetin have demonstrated health benefits due to their SIRT1 activation effects. Some structurally diverse synthetic compounds, such as SRT1720, SRT1460, Selisistat (EX 527), and AGK2 were used as small molecular SIRT modulators (IC50 = 0.04-100 μM) to treat ischemic stroke, myocardial infarction, neurodegenerative diseases, cancer, aging, and obesity. In order to get better understanding of how the small molecules interact with the sirtuin, the small molecules that having SIRT inhibitory or activation effect, found by HTS or other modern medicinal chemistry techniques, are reviewed in this article.