scholarly journals Small molecule induced toxic human-IAPP species characterized by NMR

2020 ◽  
Vol 56 (86) ◽  
pp. 13129-13132
Author(s):  
Sarah J. Cox ◽  
Diana C. Rodriguez Camargo ◽  
Young-Ho Lee ◽  
Romeo C. A. Dubini ◽  
Petra Rovó ◽  
...  
Keyword(s):  
Small Molecule ◽  
Water Soluble ◽  
Amyloid Fibers ◽  
Curcumin Derivative

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed.

scholarly journals Small Molecule Induced Toxic Human-IAPP Species Characterized by NMR

2019 ◽  
Author(s):  
Sarah J. Cox ◽  
Diana C. Rodriguez Camargo ◽  
Young-Ho Lee ◽  
Magdalena I. Ivanova ◽  
Vediappen Padmini ◽  
...  
Keyword(s):  
Small Molecule ◽  
Amyloid Β ◽  
Water Soluble ◽  
Human Calcitonin ◽  
Amyloid Fibers ◽  
Strong Interference ◽  
Curcumin Derivative

In this study, the effect of CurDAc, a water-soluble curcumin derivative, on the formation and stability of amyloid fibers is revealed. CurDAc interaction with amyloid is structurally selective which is reflected in a strong interference with hIAPP aggregation, while showing weaker interactions with human-calcitonin and Amyloid-β1-40 in comparison. Remarkably, CurDAc also exhibited potent fiber disaggregation for hIAPP generating a toxic oligomeric species.

scholarly journals Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs

Pharmaceutics ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 132 ◽  
Author(s):  
Phuong Tran ◽  
Yong-Chul Pyo ◽  
Dong-Hyun Kim ◽  
Sang-Eun Lee ◽  
Jin-Ki Kim ◽  
...  
Keyword(s):  
Anticancer Drugs ◽  
Small Molecule ◽  
Solid Dispersion ◽  
Route Of Administration ◽  
Water Soluble ◽  
Biologic Drugs ◽  
Poorly Water Soluble Drugs ◽  
Small Molecule Drugs ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble

Approximately 40% of new chemical entities (NCEs), including anticancer drugs, have been reported as poorly water-soluble compounds. Anticancer drugs are classified into biologic drugs (monoclonal antibodies) and small molecule drugs (nonbiologic anticancer drugs) based on effectiveness and safety profile. Biologic drugs are administered by intravenous (IV) injection due to their large molecular weight, while small molecule drugs are preferentially administered by gastrointestinal route. Even though IV injection is the fastest route of administration and ensures complete bioavailability, this route of administration causes patient inconvenience to visit a hospital for anticancer treatments. In addition, IV administration can cause several side effects such as severe hypersensitivity, myelosuppression, neutropenia, and neurotoxicity. Oral administration is the preferred route for drug delivery due to several advantages such as low cost, pain avoidance, and safety. The main problem of NCEs is a limited aqueous solubility, resulting in poor absorption and low bioavailability. Therefore, improving oral bioavailability of poorly water-soluble drugs is a great challenge in the development of pharmaceutical dosage forms. Several methods such as solid dispersion, complexation, lipid-based systems, micronization, nanonization, and co-crystals were developed to improve the solubility of hydrophobic drugs. Recently, solid dispersion is one of the most widely used and successful techniques in formulation development. This review mainly discusses classification, methods for preparation of solid dispersions, and use of solid dispersion for improving solubility of poorly soluble anticancer drugs.

A new water-soluble two-photon fluorescent probe for detection of trace benzoyl peroxide in wheat flour and in living cell and tissue imaging

2019 ◽  
Vol 43 (7) ◽  
pp. 3169-3173 ◽  
Author(s):  
Haiyuan Ding ◽  
Gangqiang Yuan ◽  
Liyi Zhou
Keyword(s):  
Reactive Oxygen Species ◽  
Human Health ◽  
Fluorescent Probe ◽  
Benzoyl Peroxide ◽  
Small Molecule ◽  
Living Cell ◽  
Water Soluble ◽  
Tissue Imaging ◽  
Oxygen Species ◽  
Two Photon

Benzoyl peroxide (BPO), a member of small-molecule reactive oxygen species (ROS), has attracted considerable attention because of its impact on human health and industrial importance.

scholarly journals Efficacy of a novel water soluble curcumin derivative versus Tadalafile in mediating erectile function

2015 ◽  
Vol 1 (5) ◽  
pp. 206-212
Author(s):  
SA.M. Zaahkouk ◽  
G.A Hesham ◽  
Yehia M. Hussein ◽  
H.M Atta ◽  
Fouad Hanan
Keyword(s):  
Erectile Function ◽  
Water Soluble ◽  
Curcumin Derivative

A novel, selective, orally active, potent small molecule inhibitor of Hsp90

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13067-13067 ◽  
Author(s):  
P. M. Steed ◽  
P. Fadden ◽  
S. Hall
Keyword(s):  
Body Weight ◽  
Natural Product ◽  
Small Molecule ◽  
Clinical Chemistry ◽  
Water Soluble ◽  
Tumor Growth Inhibition ◽  
Hsp90 Inhibition ◽  
Multiple Dosing ◽  
Oral Doses ◽  
Orally Active

13067 Background: The preclinical and clinical data evaluating derivatives of the natural product geldanamycin, including 17-AAG and 17-DMAG, reveal that inhibition of the molecular chaperone HSP90 results in multiple anti-tumor effects. SNX-5422 and SNX-5542 are potent, novel, highly specific, water soluble and orally active small molecule inhibitors of Hsp90. Here we describe the preclinical efficacy and toxicity evaluation of these compounds. Methods: The PK profile of SNX-5422 and SNX-5542 was determined following oral and iv dosing in mice and rats. HT29 xenografts were performed oral doses of SNX-5542 on a schedule of Q2DX3,2 for 2 weeks or 17-DMAG on the previously reported regimen of bid×5,2 for 2 weeks, with tumor progression and body weight monitored. Plasma, tumor and other tissues were harvested for evaluation of HSP70 induction and levels of HSP90 client proteins. Rats were treated with varying oral doses on a schedule of Q2DX3,2 for two weeks. Clinical observations were noted and standard hematology and clinical chemistry parameters were monitored. Results: SNX-5542 exhibited 37% oral BA in rats and >75% in mice, with t½ >7h in each species. SNX-5542 was well tolerated in normal and tumor-bearing mice at 300 mg/m2 Q2DX3,2 for 2 weeks, 0.9% weight gain. 17-DMAG at 30 mg/m2 bid×5,2 for 2 weeks caused 3.3% body weight loss. At these doses, SNX-5542 exhibited 78% median tumor growth inhibition of HT29 tumors while 17-DMAG exhibited 23% inhibition. Mechanistic indicators of HSP90 inhibition correlated with efficacy across multiple dosing levels. At 120 mg/m2 Q2DX3,2 for 2 weeks SNX-5422 was well tolerated in rats, with no significant effect on any clinical, hematology or clinical chemistry parameter with the exception of a slight increase in blood urea nitrogen levels. Histopathological evaluation of liver, thymus, spleen and kidneys revealed no significant treatment-related effects. At 120 mg/m2 Q2DX3,2 for 13 days SNX-5422 does not exhibit any of the toxicities reported for 17-DMAG (bidX5,2 for 8 days at 24 mg/m2). Conclusions: SNX small-molecule HSP90 inhibitors have favorable pharmacokinetic profiles, oral bioavailability, tolerability and superior anti-tumor activity compared to the natural product derivative 17-DMAG. [Table: see text]

scholarly journals Effect of novel water soluble curcumin derivative on experimental type- 1 diabetes mellitus (short term study)

2012 ◽  
Vol 4 (1) ◽  
Author(s):  
Mohamed T Abdel Aziz ◽  
Mohamed F El-Asmar ◽  
Ibrahim N El-Ibrashy ◽  
Ameen M Rezq ◽  
Abdulrahman L Al-Malki ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Type 1 Diabetes Mellitus ◽  
Water Soluble ◽  
Short Term ◽  
Term Study ◽  
Short Term Study ◽  
Experimental Type ◽  
Curcumin Derivative

scholarly journals Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

2013 ◽  
Vol 5 (1) ◽  
Author(s):  
Mohamed Talaat Abdel Aziz ◽  
Ibrahim Naguib El Ibrashy ◽  
Dimitri P Mikhailidis ◽  
Ameen Mahmoud Rezq ◽  
Mohamed Abdel Aziz Wassef ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Water Soluble ◽  
Signaling Mechanisms ◽  
Experimental Type ◽  
Curcumin Derivative
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