Discovery of Alkyl Triphenylphosphonium Pinostrobin Derivatives as Potent Anti-Breast Cancer Agents.

Pinostrobin demonstrated anticancer properties, but its hydrophobic feature led to a reduction in bioavailability. The mitochondria-targeted approach successfully synthesized eight new alkyl triphenylphosphonium pinostrobin derivatives (1-8) with good yield in this study. Seven compounds (1-3, 5-8) showed greater cytotoxic potency against the human MCF-7 breast cancer cell line than pinostrobin.

Synergistic effect of metformin and vitamin D on osteogenic differentiation of human adipose tissue-derived mesenchymal stem cells under high d-glucose conditions.

Introduction: Vitamin D plays a vital role in bone health, with low levels of vitamin D being related to skeletal fragility, fractures, and metabolic disorders such as diabetes. Metformin is known as an antihyperglycemic agent for regulating blood sugar. A correlation between diabetes mellitus and osteoporosis is attracting considerable interest, and research to find the prevention and treatment is gradually being studied.

Function of Burkholderia pseudomallei RpoS and RpoN2 in bacterial invasion, intracellular survival, and multinucleated giant cell formation in mouse macrophage cell line.

Melioidosis, a human infectious disease with a high mortality rate in many tropical countries, is caused by the pathogen Burkholderia pseudomallei (B. pseudomallei). The function of the B.

Preparation of self-assembly silica redox nanoparticles to improve drug encapsulation and suppress the adverse effect of doxorubicin.

Background And Purpose: The utilization of doxorubicin (DOX) in clinal trials is also challenging owing to its adverse effects, including low oral bioavailability, generation of reactive oxygen species (ROS), cardiotoxicity, and epithelial barrier damage. Recently, scavenging of ROS reduced the cytotoxicity of DOX, suggesting a new approach for using DOX as an anticancer treatment. Thus, in this study, non-silica and silica redox nanoparticles (denoted as RNP and siRNP, respectively) with ROS scavenging features have been designed to encapsulate DOX and reduce its cytotoxicity.

,2,6-Trisubstituted 1-benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents: design, synthesis, evaluation, and studies.

Compounds containing benzimidazole moiety occupy privileged chemical space for discovering new bioactive substances. In continuation of our recent work, 69 benzimidazole derivatives were designed and synthesized with good to excellent yields of 46-99% using efficient synthesis protocol sodium metabisulfite catalyzed condensation of aromatic aldehydes with -phenylenediamines to form 2-arylbenzimidazole derivatives followed by -alkylation by conventional heating or microwave irradiation for diversification. Potent antibacterial compounds against MSSA and MRSA were discovered such as benzimidazole compounds 3k (2-(4-nitrophenyl), -benzyl), 3l (2-(4-chlorophenyl), -(4-chlorobenzyl)), 4c (2-(4-chlorophenyl), 6-methyl, -benzyl), 4g (2-(4-nitrophenyl), 6-methyl, -benzyl), and 4j (2-(4-nitrophenyl), 6-methyl, -(4-chlorobenzyl)) with MIC of 4-16 μg mL.

Synthesis, Biological Evaluation, and Molecular Modeling Studies of 1-Aryl-1-pyrazole-Fused Curcumin Analogues as Anticancer Agents.

Addressing the growing burden of cancer and the shortcomings of chemotherapy in cancer treatment are the current research goals. Research to overcome the limitations of curcumin and to improve its anticancer activity via its heterocycle-fused monocarbonyl analogues (MACs) has immense potential. In this study, 32 asymmetric MACs fused with 1-aryl-1-pyrazole () were synthesized and characterized to develop new curcumin analogues.

Sorafenib-loaded silica-containing redox nanoparticles for oral anti-liver fibrosis therapy.

Liver fibrosis is a chronic disease resulting from repetitive or prolonged liver injury with limited treatment options. Sorafenib has been reported to be a potential antifibrotic agent; however, its therapeutic effect is restricted because of its low bioavailability and severe adverse effects in the gastrointestinal (GI) tract. In this study, we developed sorafenib-loaded silica-containing redox nanoparticles (sora@siRNP) as an oral nanomedicine to treat liver fibrosis.

A silica-based antioxidant nanoparticle for oral delivery of Camptothecin which reduces intestinal side effects while improving drug efficacy for colon cancer treatment.

Camptothecin (CPT) is a potent anticancer agent for the treatment of colorectal cancer; however, it exhibits some limitations, including poor solubility, low stability, and low bioavailability via oral administration, which restrict its usability in clinical treatments. In addition, overproduction of reactive oxygen species (ROS) during chemotherapy induces drug resistance and severe intestinal side effects. In this study, silica-installed ROS scavenging nanoparticles (siRNP) with 50-60 nm in diameter were employed to overcome the aforementioned drawbacks of CPT.

Nitric Oxide Nano-Delivery Systems for Cancer Therapeutics: Advances and Challenges.

Nitric oxide (NO) plays important roles in various physiological and pathological functions and processes in the human body. Therapeutic application of NO molecules has been investigated in various diseases, including cardiovascular disease, cancer, and infections. However, the extremely short half-life of NO, which limits its clinical use considerably, along with non-specific distribution, has resulted in a low therapeutic index and undesired adverse effects.

Design of amino acid-based self-assembled nano-drugs for therapeutic applications.

Amino acids have attracted considerable attention in drug development because they play important roles in many physiological and pathological processes. In the past several decades, various amino acid supplementations have been reported to have potential therapeutic efficacy for the treatment of many disorders in clinical trials. However, their effectiveness is controversially reported, which may be explained by poor pharmacokinetic properties of such low-molecular-weight agents.

Self-assembled polydopamine nanoparticles improve treatment in Parkinson's disease model mice and suppress dopamine-induced dyskinesia.

Although Levodopa (l-DOPA), a dopamine precursor, exhibits a high risk of dyskinesia, it remains the primary treatment in Parkinson's disease (PD), a progressive neurodegenerative disorder. In this study, we designed poly(l-DOPA)-based self-assembled nanodrug (Nano) from amphiphilic block copolymer possessing poly(l-DOPA(OAc)), which is a precursor of l-DOPA as a hydrophobic segment, for treatment in a PD model mouse. Under physiological enzyme treatment, the poly(l-DOPA(OAc)) in the block copolymer was hydrolyzed to liberate l-DOPA gradually.

Poly(ornithine)-based self-assembling drug for recovery of hyperammonemia and damage in acute liver injury.

Oligo-peptides, including monomeric amino acids, have received much attention as bioactive molecules and drugs. One of the biggest problems of these compounds, however, is their very short bioavailability due to instant metabolism and rapid excretion. To solve this problem, we newly designed a poly(ethylene glycol) (PEG)-block-polypeptide self-assembling based drug for the treatment of acute liver injury.

Encapsulation of tissue plasminogen activator in pH-sensitive self-assembled antioxidant nanoparticles for ischemic stroke treatment - Synergistic effect of thrombolysis and antioxidant.

The medical treatment for stroke has advanced greatly in recent years. Thrombolytic therapy with tissue plasminogen activator (t-PA) is one of the mainstream treatments, but it still has many problems, including short half-life, and t-PA-induced reperfusion and oxidative injuries. To broaden the therapeutic window of t-PA and reduce its associated oxidative stress after reperfusion, t-PA-installed, nitroxide radical-containing, self-assembled polyion complex nanoparticles (t-PA@iRNP) were designed.

Novel angiogenesis therapeutics by redox injectable hydrogel - Regulation of local nitric oxide generation for effective cardiovascular therapy.

Nitric oxide (NO) possesses various functions in cardiovascular diseases; however, due to an extremely short half-life and low bioavailability, its therapeutic application is limited. In inflamed tissues, overproduced reactive oxygen species (ROS) rapidly react with the endogenous NO, reducing its bioavailability. Here, we developed a controllable NO-releasing redox injectable hydrogel (NO-RIG) formed by the electrostatic crosslinking between the polyion complex flower-type micelles composing of functional polymers to scavenge overproduced ROS and regulate the local NO expression level simultaneously.

Newly Designed Silica-Containing Redox Nanoparticles for Oral Delivery of Novel TOP2 Catalytic Inhibitor for Treating Colon Cancer.

Although oral drug delivery is the most common route of drug administration, the conventional polymeric nanocarriers exhibit a low drug loading capacity and low stability in the gastrointestinal (GI) environments. In this study, a newly designed silica-containing redox nanoparticle (siRNP) with reactive oxygen species (ROS) scavenging capacity is developed as an ideal oral nanocarrier for a novel hydrophobic anticancer compound BNS-22 to treat colitis-associated colon cancer in vivo. Crosslinking of silica moieties significantly enhances the stability under acidic conditions and improves BNS-22 loading capacity of siRNP compared to the conventional redox nanoparticle.

Chronic treatment with a smart antioxidative nanoparticle for inhibition of amyloid plaque propagation in Tg2576 mouse model of Alzheimer's disease.

The present study aimed to assess whether our newly developed redox nanoparticle (RNP) that has antioxidant potential decreases Aβ levels or prevents Aβ aggregation associated with oxidative stress. The transgenic Tg2576 Alzheimer's disease (AD) mice were used to investigate the effect of chronic ad libitum drinking of RNP solution for 6 months, including memory and learning functions, antioxidant activity, and amyloid plaque aggregation. The results showed that RNP-treated mice had significantly attenuated cognitive deficits of both spatial and non-spatial memories, reduced oxidative stress of lipid peroxide, and DNA oxidation.

Evaluation of the Toxicity and Antioxidant Activity of Redox Nanoparticles in Zebrafish (Danio rerio) Embryos.

Recently, we have been developing polymer and nanoparticle-based antioxidative nanotherapeutics. Our strategy is to eliminate overproduced reactive oxygen species (ROS), which are strongly related to various diseases. In order to facilitate the transition of the nanotherapeutics into clinical studies, we investigated the toxicity and antioxidant activity of our nanoparticles in a zebrafish model.

Combination Treatment of Murine Colon Cancer with Doxorubicin and Redox Nanoparticles.

Conventional chemotherapeutic drugs such as doxorubicin (DOX) are associated with severe adverse effects such as cardiac, hepatic, and gastrointestinal (GI) toxicities. Excessive production of reactive oxygen species (ROS) was reported to be one of the main mechanisms underlying these severe adverse effects. Recently, we have developed 2 types of novel redox nanoparticles (RNPs) including pH-sensitive redox nanoparticle (RNP(N)) and pH-insensitive redox nanoparticle (RNP(O)), which effectively scavenge overproduced ROS in inflamed and cancerous tissues.

Redox nanoparticles as a novel treatment approach for inflammation and fibrosis associated with nonalcoholic steatohepatitis.

Aim: Oxidative stress (OS) is largely thought to be a central mechanism responsible for liver damage, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Our aim was to investigate whether suppression of OS in the liver via redox nanoparticles (RNPs) reduces liver damage in a mouse model of NASH.

Materials & Methods: RNPs were prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals and were orally administered by daily gavage for 4 weeks.

Specific accumulation of orally administered redox nanotherapeutics in the inflamed colon reducing inflammation with dose-response efficacy.

Although current medications for ulcerative colitis (UC) are effective to some extent, there are still some limitation of their use due to the non-specific distribution, drug metabolism in the gastrointestinal tract, and severe adverse effects. In our previous studies, we developed oral redox nanoparticles (RNP(O)) that specifically accumulated and scavenged overproduced reactive oxygen species (ROS) in an inflamed colon. However, the mechanism leading to specific accumulation of RNP(O) in an inflamed colon is still unclear.

Recovery of Cognitive Dysfunction via Orally Administered Redox-Polymer Nanotherapeutics in SAMP8 Mice.

Excessively generated reactive oxygen species are associated with age-related neurodegenerative diseases. We investigated whether scavenging of reactive oxygen species in the brain by orally administered redox nanoparticles, prepared by self-assembly of redox polymers possessing antioxidant nitroxide radicals, facilitates the recovery of cognition in 17-week-old senescence-accelerated prone (SAMP8) mice. The redox polymer was delivered to the brain after oral administration of redox nanoparticles via a disintegration of the nanoparticles in the stomach and absorption of the redox polymer at small intestine to the blood.

Development of an oral nanotherapeutics using redox nanoparticles for treatment of colitis-associated colon cancer.

Oral chemotherapy is the preferred treatment for colon cancer. However, this strategy faces many challenges, including instability in the gastrointestinal (GI) tract, insufficient bioavailability, low tumor targeting, and severe adverse effects. In this study, we designed a novel redox nanoparticle (RNP(O)) that is an ideal oral therapeutics for colitis-associated colon cancer treatment.