Potent telomerase activators from a novel sapogenin via biotransformation utilizing Camarosporium laburnicola, an endophytic fungus.

Background: Cycloartane-type triterpenoids possess important biological activities, including immunostimulant, wound healing, and telomerase activation. Biotransformation is one of the derivatization strategies of natural products to improve their bioactivities. Endophytic fungi have attracted attention in biotransformation studies because of their ability to perform modifications in complex structures with a high degree of stereospecificity.

Design, synthesis, and biological evaluation of some novel naphthoquinone-glycine/β-alanine anilide derivatives as noncovalent proteasome inhibitors.

A series of novel noncovalent glycine/β-alanine anilide derivatives possessing 2-chloronaphthoquinone structure as a pharmacophoric unit were designed, synthesized, and evaluated for their antiproliferative and antiproteasomal activities against MCF-7 cell line, in vitro. According to biological activity results, all the target compounds showed antiproliferative activity in the range of IC  = 7.10 ± 0.

The role of cycloastragenol at the intersection of NRF2/ARE, telomerase, and proteasome activity.

Aging is well-characterized by the gradual decline of cellular functionality. As redox balance, proteostasis, and telomerase systems have been found to be associated with aging and age-related diseases, targeting these systems with small compounds has been considered a promising therapeutic approach. Cycloastragenol (CA), a small molecule telomerase activator obtained from Astragalus species, has been reported to positively affect several age-related pathophysiologies, but the mechanisms underlying CA activity have yet to be reported.

Novel regulation mechanism of adrenal cortisol and DHEA biosynthesis via the endogen ERAD inhibitor small VCP-interacting protein.

Endoplasmic reticulum-associated degradation (ERAD) is a well-characterized mechanism of protein quality control by removal of misfolded or unfolded proteins. The tight regulation of ERAD is critical for protein homeostasis as well as lipid metabolism. Although the mechanism is complex, all ERAD branches converge on p97/VCP, a key protein in the retrotranslocation step.

A new underlying mechanism for the neuroprotective effect of bosutinib: Reverting toxicity-induced PARylation in SIN1-mediated neurotoxicity.

Increased levels of reactive oxygen and nitrogen species play an important role in the development and progression of neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. The overproduction of these highly reactive chemical species leads to DNA damage and subsequent activation of the poly(ADP-ribose)polymerase (PARP) enzyme. Several studies have demonstrated the potential use of PARP inhibitors for neuroprotection.

Induction of Divergent Cell Death Pathways by Urea and Carbohydrazide Derivatives.

Background: The complexity of cancer biology and the development of chemotherapy resistance are two main obstacles to cancer treatment and necessitate novel anticancer molecules that target different cell death pathways. Modulation of Endoplasmic Reticulum (ER) stress and subsequent activation of the Unfolded Protein Response (UPR) has been proposed as a potential chemotherapeutic target, as prolonged ER stress can lead to cell death via apoptosis or necrosis.

Objective: The present study aims to evaluate the molecular mechanism underlying the cytotoxic activity of selected urea and carbohydrazide derivatives.

Telomerase activators from 20(27)-octanor-cycloastragenol via biotransformation by the fungal endophytes.

Cycloastragenol [20(R),24(S)-epoxy-3β,6α,16β,25-tetrahydroxycycloartane] (CA), the principle sapogenol of many cycloartane-type glycosides found in Astragalus genus, is currently the only natural product in the anti-aging market as telomerase activator. Here, we report biotransformation of 20(27)-octanor-cycloastragenol (1), a thermal degradation product of CA, using Astragalus species originated endophytic fungi, viz. Penicillium roseopurpureum, Alternaria eureka, Neosartorya hiratsukae and Camarosporium laburnicola.

Design, synthesis and biological evaluation of novel naphthoquinone-4-aminobenzensulfonamide/carboxamide derivatives as proteasome inhibitors.

A series of novel 4-aminobenzensulfonamide/carboxamide derivatives bearing naphthoquinone pharmacophore were designed, sythesized and evaluated for their proteasome inhibitory and antiproliferative activities against human breast cancer cell line (MCF-7). The structures of the synthesized compounds were confirmed by spectral and elemental analyses. The proteasome inhibitory activity studies were carried out using cell-based assay.

Microbial Transformation of Cycloastragenol and Astragenol by Endophytic Fungi Isolated from Species.

Biotransformation of sapogenins (cycloastragenol () and astragenol ()) by species originated endophytic fungi resulted in the production of five new metabolites (, , , , ) together with 10 known compounds. The structures of the new compounds were established by NMR spectroscopic and HRMS analysis. Oxygenation, oxidation, epoxidation, dehydrogenation, and ring cleavage reactions were observed on the cycloartane (9,19-cyclolanostane) nucleus.

Polyethers isolated from the marine actinobacterium Streptomyces cacaoi inhibit autophagy and induce apoptosis in cancer cells.

Polyether compounds, a large group of biologically active metabolites produced by Streptomyces species have been reported to show a variety of bioactivity such as antibacterial, antifungal, antiparasitic, antiviral, and tumour cell cytotoxicity. Since some of these compounds target cancer stem cells and multi-drug resistant cancer cells, this family of compounds have become of high interest. In this study, three polyether-type metabolites (1-3), one of which was a new natural product (3), were isolated from the marine derived Streptomyces cacaoi via antimicrobial activity-guided fractionation studies.

83 W, 3.1 MHz, square-shaped, 1 ns-pulsed all-fiber-integrated laser for micromachining.

We demonstrate an all-fiber-integrated laser based on off-the-shelf components producing square-shaped, 1 ns-long pulses at 1.03 μm wavelength with 3.1 MHz repetition rate and 83 W of average power.