Semisynthetic derivatives of the fungal metabolite eupenifeldin via targeting the tropolone hydroxy groups.

Eupenifeldin (1) is a fungal secondary metabolite possessing bis-tropolone moieties that demonstrates nanomolar cytotoxic activity against a number of cancer cell types. As a potential anticancer lead, this meroterpenoid was used to access 29 semisynthetic analogues via functionalization of the reactive hydroxy groups of the bis-tropolones. A series of ester (2-6), carbonate (7-8), sulfonate (9-16), carbamate (17-20), and ether (21-30) analogues of 1 were generated via 22 reactions.

Probing the Cytotoxic Signaling Induced by Eupenifeldin in Ovarian Cancer Models.

High-grade serous ovarian cancer (HGSOC) is the most common and lethal ovarian cancer histotype. Lack of early detection methods, limited therapeutic agents, and low 5-year survival rate reflect the urgent need to develop new therapies. Eupenifeldin, a bistropolone, originally isolated from , is a cytotoxic fungal metabolite.

The effects of statin therapy on brain tumors, particularly glioma: a review.

Brain tumors account for less than 2% of all malignancies. However, they are associated with the highest morbidity and mortality rates among all solid tumors. The most common malignant primary brain tumors are glioma or glioblastoma (GBM), which have a median survival time of about 14 months, often suffer from recurrence after a few months following treatment, and pose a therapeutic challenge.

Embellicines C-E: Macrocyclic Alkaloids with a Cyclopenta[b]fluorene Ring System from the Fungus sp.

Macrocyclic alkaloids with a cyclopenta[b]fluorene ring system are a relatively young structural class of fungal metabolites, with the first members reported in 2013. Bioassay-guided fractionation of a sp. (fungal strain MSX6737) led to a series of both known and new members of this structural class (-), including the known embellicine A (), three new embellicine analogues (, , and ), and a semisynthetic acetylated analogue ().

Lipid Nanoparticle Delivery of Fas Plasmid Restores Fas Expression to Suppress Melanoma Growth .

Fas ligand (FasL), expressed on the surface of activated cytotoxic T lymphocytes (CTLs), is the physiological ligand for the cell surface death receptor, Fas. The Fas-FasL engagement initiates diverse signaling pathways, including the extrinsic cell death signaling pathway, which is one of the effector mechanisms that CTLs use to kill tumor cells. Emerging clinical and experimental data indicate that Fas is essential for the efficacy of CAR-T cell immunotherapy.

Semisynthesis of Hypothemycin Analogues Targeting the C8-C9 Diol.

Hypothemycin, an epoxide derivative of (5)-7-oxozeaenol, was used in the semisynthesis of a series of C8-C9 diol derivatives, with many inhibiting TAK1 at submicromolar concentrations. A step-economical approach was chosen, whereby nonselective reactions functionalized the diol to generate multiple analogues in a single reaction. Using this approach, 35 analogues were synthesized using 12 reactions, providing a wealth of information about the role that the C8-C9 diol plays in TAK1 inhibition and cytotoxicity in ovarian and breast cancer cell lines.

Structural Diversity of Perylenequinones Is Driven by Their Redox Behavior.

Hypocrellins and hypomycins are two subclasses of fungal perylenequinones with unique structural, biological, and photochemical properties. With the growing interest in these naturally occurring photosensitizers, more studies were warranted to better understand the structural relationships between these two subclasses of perylenequinones. In this study, the long-postulated biosynthetic precursor () of class B fungal perylenequinones was isolated and characterized from a -like sp.

Dereplication of Fungal Metabolites by NMR-Based Compound Networking Using MADByTE.

Strategies for natural product dereplication are continually evolving, essentially in lock step with advances in MS and NMR techniques. MADByTE is a new platform designed to identify common structural features between samples in complex extract libraries using two-dimensional NMR spectra. This study evaluated the performance of MADByTE for compound dereplication by examining two classes of fungal metabolites, the resorcylic acid lactones (RALs) and spirobisnaphthalenes.

Researchers' ethical perspective about women participation in research studies in Jordan.

Women participation in research studies has been an issue especially in developing countries with conservative cultural and religious beliefs. This study was aimed to assess researchers about ethical and cultural issues related to the women participation in research studies. A descriptive cross-sectional questionnaire-based survey was conducted among researchers from different health disciplines in Jordan.

Three diketomorpholines from a Penicillium sp. (strain G1071).

Three previously undescribed diketomorpholine natural products, along with the known phenalenones, herqueinone and norherqueinone, were isolated from the mycoparasitic fungal strain G1071, which was identified as a Penicillium sp. in the section Sclerotiora. The structures were established by analyzing NMR data and mass spectrometry fragmentation patterns.

Media and strain studies for the scaled production of cis-enone resorcylic acid lactones as feedstocks for semisynthesis.

Resorcylic acid lactones (RALs) with a cis-enone moiety, represented by hypothemycin (1) and (5Z)-7-oxozeaenol (2), are fungal secondary metabolites with irreversible inhibitory activity against protein kinases, with particularly selective activity for inhibition of TAK1 (transforming growth factor beta-activated kinase 1). Gram-scale quantities of these compounds were needed as feedstock for semi-synthesizing RAL-analogues in a step-economical fashion. To do so, this study had three primary goals: identifying fungi that biosynthesized 1 and 2, enhancing their production by optimizing the fermentation conditions on the lab scale, and developing straight forward purification processes.

Thielavins: tuned biosynthesis and LR-HSQMBC for structure elucidation.

A series of thielavins I, V, and Q (1-3) and the previously undescribed thielavin Z (4) were isolated from cultures of a fungal Shiraia-like sp. (strain MSX60519) that were grown under a suite of media and light conditions, with enhanced biosynthesis noted using rice as a substrate with 12:12 h light:dark cycles. Conversely, oatmeal medium and continuous white light-emitting diode light exposure negatively affected the production of these compounds, at least by strain MSX60519.

Delivery of eupenifeldin via polymer-coated surgical buttresses prevents local lung cancer recurrence.

Lung cancer is the leading cause of cancer deaths worldwide. Unfortunately, high recurrence rates and poor survival remain despite surgical resection and conventional chemotherapy. Local drug delivery systems are a promising intervention for lung cancer treatment with the potential for improved efficacy with reduced systemic toxicity.

Enhanced Production and Anticancer Properties of Photoactivated Perylenequinones.

Hypocrellins and hypomycins are naturally occurring fungal perylenequinones with potential photodynamic activity against cancer and microbial diseases. This project pursued three lines of research. First, the production of perylenequinones was enhanced by investigating the effect of culture medium and light exposure on their biosynthesis.

Molecular targets for the interactive effect of etazolate during post-traumatic stress disorder: Role of oxidative stress, BDNF and histones.

Post-traumatic stress disorder (PTSD) develops in individuals after exposure to severe, life-threatening traumatic event. Etazolate is a selective phosphodiesterase IV inhibitor that is highly specific for cAMP, which has anxiolytic and antidepressant effects. We have previously shown that PTSD induced-memory impairment, anxiety and depression were prevented via the administration of etazolate.

Silymarin Prevents Memory Impairments, Anxiety, and Depressive-Like Symptoms in a Rat Model of Post-Traumatic Stress Disorder.

Post-traumatic stress disorder (PTSD) is a debilitating psychopathological disease that is triggered by exposure to traumatic events. It is usually associated with substantial comorbidities, such as cognitive impairment, anxiety, and depression. Silymarin has been recently reported to exert neuroprotective activities against neurodegenerative diseases such as Alzheimer's and Parkinson's diseases.

Evaluating the protective effect of etazolate on memory impairment, anxiety- and depression-like behaviors induced by post traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder that develops after an individual experiences severe life-threatening traumatic stress. Etazolate is a selective phosphodiesterase-4 inhibitor that is specific for cAMP. Etazolate showed anxiolytic and antidepressant activity, and could be useful in managing PTSD co-morbidities.