Ugi Adducts as Novel Anti-austerity Agents against PANC-1 Human Pancreatic Cancer Cell Line: A Rapid Synthetic Approach.

Pancreatic cancer cells have an inherent tolerance to withstand nutrition starvation, allowing them to survive in hypovascular tumor microenvironments that lack of sufficient nutrients and oxygen. Developing anti-cancer agents that target this tolerance to nutritional starvation is a promising anti-austerity strategy for eradicating pancreatic cancer cells in their microenvironment. In this study, we employed a chemical biology approach using the Ugi reaction to rapidly synthesize new anti-austerity agents and evaluate their structure-activity relationships.

Piper longum Constituents Induce PANC-1 Human Pancreatic Cancer Cell Death under Nutrition Starvation.

Pancreatic cancer is a highly aggressive form of cancer with a poor prognosis, partly due to 'austerity', a phenomenon of tolerance to nutrient deprivation and survival in its hypovascular tumor microenvironment. Anti-austerity agents which preferentially diminish the survival of cancer cells under nutrition starvation is regarded as new generation anti-cancer agents. This study investigated the potential of Piper longum constituents as anti-austerity agents.

Targeting Pancreatic Cancer with Novel Plumbagin Derivatives: Design, Synthesis, Molecular Mechanism, and Evaluation.

Pancreatic tumors grow in an "austerity" tumor microenvironment characterized by nutrient deprivation and hypoxia. This leads to the activation of adaptive pathways in pancreatic cancer cells, promoting tolerance to nutrition starvation and aggressive malignancy. Conventional anticancer drugs are often ineffective against tumors that grow in such austerity condition.

Structure-activity relationship and mechanistic study on guggulsterone derivatives; Discovery of new anti-pancreatic cancer candidate.

Pancreatic cancer is one of the deadliest types of malignancies. A new intervention aiming to combat pancreatic cancer is targeting its extra-ordinary ability to tolerate nutrition starvation, a phenomenon known as "Austerity". As a part of a research program aiming to develop a new-generation of anticancer agents, known as "anti-austerity agents", guggulsterone derivatives (GSDs) were identified as unique anti-austerity agents in terms of potency and selectivity.

GDP Induces PANC-1 Human Pancreatic Cancer Cell Death Preferentially under Nutrient Starvation by Inhibiting PI3K/Akt/mTOR/Autophagy Signaling Pathway.

Pancreatic tumors are hypovascular, which leads to a poor nutrient supply to support the aggressively proliferating tumor cells. However, human pancreatic cancer cells have extreme resistance to nutrition starvation, which enables them to survive under severe metabolic stress conditions within the tumor microenvironment, a phenomenon known as "austerity" in cancer biology. Discovering agents which can preferentially inhibit the cancer cells' ability to tolerate starvation conditions represents a new generation of anticancer agents.

PPARα Agonist, MHY3200, Alleviates Renal Inflammation during Aging via Regulating ROS/Akt/FoxO1 Signaling.

PPARα is a ligand-dependent transcription factor and its activation is known to play an important role in cell defense through anti-inflammatory and antioxidant effects. MHY3200 (2-[4-(5-chlorobenzo[]thiazol-2-yl)phenoxy]-2,2-difluoroacetic acid), a novel benzothiazole-derived peroxisome proliferator-activated receptor α (PPARα) agonist, is a synthesized PPARα activator. This study examined the beneficial effects of MHY3200 on age-associated alterations in reactive oxygen species (ROS)/Akt/forkhead box (FoxO) 1 signaling in rat kidneys.

Benzylisoquinoline alkaloids from Gaertn. petals with antiausterity activities against the HeLa human cervical cancer cell line.

Ethanolic extract of petals showed preferential cytotoxic activity against HeLa human cervical cancer cell line with a PC value of 10.4 μg/mL. This active extract was subjected to a phytochemical investigation study which led to the isolation of nine benzylisoquinoline alkaloids (-).

Benzophenones from with Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Cell Line.

The antiausterity strategy is a promising approach for the discovery of lead compounds with unprecedented anticancer activities by targeting the tolerance of cancer cells to nutrition starvation. These agents are selectively cytotoxic under the tumor microenvironment-mimicking condition of nutrition starvation, without apparent toxicity in the normal nutrient-rich condition. In this study, an ethanol extract of showed antiausterity activity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC value of 13.

Chemical constituents of Thai Piper ribesoides and their antiausterity activities against the PANC-1 human pancreatic cancer cell line.

A methanolic extract of Thai Piper ribesoides showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition, with a PC value of 24 μg/mL. Phytochemical investigation of this bio-active extract led to the isolation of six compounds (1-6), including two new polyoxygenated cyclohexane derivatives, named ribesoidones A and B (1 and 2). The structural elucidation of the new compounds was achieved by a combination of HREIMS, NMR, and circular dichroism spectroscopic analyses.

A new anti-austerity agent, 4'-O-methylgrynullarin from Derris scandens induces PANC-1 human pancreatic cancer cell death under nutrition starvation via inhibition of Akt/mTOR pathway.

An ethanolic extract of Derris scandens flowers showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived condition, with a PC value of 0.7 μg/mL. Phytochemical investigation of this active extract led to the isolation of four prenylated isoflavones (1-4) including a new compound named 4'-O-methylgrynullarin (1).

Anti-Austerity Activity of Thai Medicinal Plants: Chemical Constituents and Anti-Pancreatic Cancer Activities of .

Human pancreatic tumor cells have an intrinsic ability to tolerate nutrition starvation and survive in the hypovascular tumor microenvironment, the phenomenon termed as "austerity". Searching for an agent that inhibits such tolerance to nutrient starvation and kills the pancreatic cancer cells preferentially in nutrient-starvation is a unique anti-austerity strategy in anti-cancer drug discovery. In this strategy, plant extracts and compounds are tested against PANC-1 human pancreatic cancer cell line under the conditions of nutrient-deprived medium (NDM) and nutrient-rich medium (DMEM), to discover the compounds that show selective cytotoxicity in NDM.

A new flavanone derivative from the rhizomes of .

From the methanolic extract of the rhizomes of , a new flavanone derivative named (2,7″)-8-(1-phenyl-2-carboxyethyl)pinocembrin () and four known flavonoids (-) were isolated. Its absolute configuration was concluded by NMR and MS spectroscopic analysis, together with comparison between experimental and calculated ECD data. In turn, compound exhibited strong cytotoxicity against the PANC-1 human pancreatic cancer cell line with a PC value of 6.

Short-term intake of high fat diet aggravates renal fibrosis in aged Sprague-Dawley rats.

Age- or high fat diet (HFD)-associated renal structural changes are commonly associated with a decline in renal function. Although HFD causes injurious effects in various organs during aging, its effects on age-associated renal fibrosis have not yet been investigated. In this study, we show that a short-term HFD significantly induces renal fibrosis by causing loss of mitochondrial integrity in aged Sprague-Dawley (SD) rats.

A Triterpene Lactone from Callistemon citrinus Inhibits the PANC-1 Human Pancreatic Cancer Cells Viability through Suppression of Unfolded Protein Response.

Human pancreatic tumor cells such as PANC-1 are known for their ability to tolerate nutrient starvation and thrive under the hypovascular tumor microenvironment, a phenomenon termed as 'austerity'. A search of agents that preferentially inhibit the cancer cell viability under the starvation condition without toxicity in the nutrient-rich condition is a promising approach in anticancer drug discovery. In this study, a triterpene lactone, 3β-hydroxy-13,28-epoxyurs-11-en-28-one (ursenolide), isolated from a Callistemon citrinus extract has shown strong preferential cytotoxicity against PANC-1 cells under nutrient starvation with PC value of 0.

Chemical constituents of Callistemon citrinus from Egypt and their antiausterity activity against PANC-1 human pancreatic cancer cell line.

Human pancreatic cancer is resistant to almost all conventional chemotherapeutic agents. It is known to proliferate aggressively within hypovascular tumor microenvironment by exhibiting remarkable tolerance to nutrition starvation,  a phenomenon termed as "austerity". Search for the new agents that eliminate the tolerance of cancer cells to nutrition starvation is a promising strategy in anticancer drug discovery.

Highly Potent Antiausterity Agents from and Their Mechanism of Action against the PANC-1 Human Pancreatic Cancer Cell Line.

Human pancreatic cancer cells display remarkable tolerance to nutrition starvation that help them to survive in a hypovascular tumor microenvironment, a phenomenon known as "austerity". The elucidation of agents countering this tolerance is an established antiausterity strategy in anticancer drug discovery. In this study, a leaf extract inhibited the viability of PANC-1 human pancreatic cancer cells preferentially under nutrient-deprived medium (NDM) with a PC value of 7.

Fragranone C: a new dihydrochalcone glucopyranoside from twigs.

A phytochemical investigation of an ethanolic extract of twigs collected from Thailand resulted in the discovery of a new dihydrochalcone glucopyranoside named fragranone C (), together with six previously reported compounds. The structural elucidation of the new compound was achieved by HRFABMS, NMR spectroscopic analysis and acid hydrolysis.[Figure: see text].

Safflower seed extract synergizes the therapeutic effect of cisplatin and reduces cisplatin-induced nephrotoxicity in human colorectal carcinoma RKO cells and RKO-transplanted mice.

Safflower seed is effective against oxidative stress, mediating the activation of the apoptotic signaling pathway in the renal tissues of cisplatin-treated mice. The anticancer activity of safflower in various cancer cell lines has also been reported. The present study was conducted to evaluate the potential synergistic anticancer effects of the co-treatment of safflower seed extracts and cisplatin in RKO cells and in BALB/c mice bearing RKO cell-derived human colorectal tumors.

Chemical constituents from and their antiausterity activities against the PANC-1 human pancreatic cancer cell line.

The 70% ethanolic extract of showed preferential cytotoxicity against PANC-1 human pancreatic cancer cells under a nutrient-deprived condition with PC 12.5 μg/mL. A phytochemical investigation of this extract yielded a new bicyclic [4:3:0] sesquiterpene named (+)-vulgaric acid (), together with eight previously reported compounds.

Safflower (Carthamus tinctorius L.) seed attenuates memory impairment induced by scopolamine in mice via regulation of cholinergic dysfunction and oxidative stress.

Cholinergic dysfunction and oxidative stress are the most common causes of Alzheimer's disease (AD). Safflower seed contains various anti-oxidant and cholinergic improvement compounds, such as serotonin and its derivatives. In the present study, we investigated the protective effects and mechanisms of a safflower seed extract on scopolamine-induced memory impairment in a mouse model.

Protective Effects of Serotonin and its Derivatives, N-Feruloylserotonin and N-(p-Coumaroyl) Serotonin, Against Cisplatin-Induced Renal Damage in Mice.

This study examined whether serotonin and two of its derivatives, -feruloylserotonin and -( -coumaroyl) serotonin, have a renoprotective effect in a mouse model of cisplatin-induced acute renal failure. Cisplatin (20 mg/kg body weight) was administered by intraperitoneal injection to male BALB/c mice that had received oral serotonin, -feruloylserotonin or -( -coumaroyl) serotonin (7.5 mg/kg body weight per day) during the preceding 2 days.

Hepatoprotective Effects of MHY3200 on High-Fat, Diet-Induced, Non-Alcoholic Fatty Liver Disease in Rats.

This study investigated the effects of 2-(4-(5-chlorobenzo[]thiazol-2-yl)phenoxy)-2,2-difluoroacetic acid (MHY3200) on high-fat diet (HFD)-induced hepatic lipid accumulation and inflammation. The measurement of peroxisome proliferator-activated receptor (PPAR)α activity by using a luciferase assay indicated that MHY3200 was more potent than a known PPARα agonist, WY14643, in AC2F cells. Six-month-old male SD rats were fed chow or HFD for 1 month, and after, with or without added MHY3200 (1 or 2 mg/kg/day) for 4 weeks.

Novel SIRT1 activator MHY2233 improves glucose tolerance and reduces hepatic lipid accumulation in db/db mice.

The NAD-dependent deacetylase SIRT1, which is associated with the improvement of metabolic syndromes, such as type 2 diabetes, is a well-known longevity-related gene. Several in vitro and in vivo studies have shown the known protective effects of SIRT1 activators, such as resveratrol and SRT1720, on diabetes- or obesity-induced fatty liver and insulin resistance. Here, we newly synthesized 18 benzoxazole hydrochloride derivatives based on the structure of resveratrol and SRT1720.

Thio-barbiturate-derived compounds are novel antioxidants to prevent LPS-induced inflammation in the liver.

Liver inflammation is closely associated with metabolic syndrome. Oxidative stress plays a synergistic role in inflammation by activating nuclear factor kappa B (NF-κB) signaling in the liver. Therefore, substantial efforts have been made to develop compounds that inhibit the generation of oxidative stress and activation of NF-κB.