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Medicinal-Pharmaceutical Chemistry Commons

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Articles 1 - 7 of 7

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

A Novel Bromodomain And Extra-Terminal Domain Inhibitors (Beti) That Reverses Hiv-1 Latency, Shuai Liu, Maxime Jean, Wei Zhang, Jian Zhu May 2017

A Novel Bromodomain And Extra-Terminal Domain Inhibitors (Beti) That Reverses Hiv-1 Latency, Shuai Liu, Maxime Jean, Wei Zhang, Jian Zhu

UMass Center for Clinical and Translational Science Research Retreat

Although combinatory antiretroviral therapy (cART) is effective to reduce HIV-1 viremia, it does not eliminate HIV-1 infection. HIV-1 remains latent with the presence of cART, impeding the cure of AIDS. Recently, latency-reversing agents (LRAs) have been developed to purge latent HIV-1, providing an intriguing strategy for eradication of residual, latent viral reservoirs. Our earlier studies show that antagonism of HIV-1 competitive factor bromodomain containing 4 (BRD4) using bromodomain and extra-terminal domain inhibitor (BETi) JQ1 may facilitate the reversal of HIV-1 latency. BETis have recently emerged as a class of compounds that are promising for both the anticancer and HIV-1 latency-reversing ...


Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian May 2016

Crystal Protein Cry5b As A Novel And Powerful Anthelmintic, David Koch, Zeynep Mirza, Yan Hu, Thanh-Thanh Nguyen, Gary R. Ostroff, Raffi V. Aroian

UMass Center for Clinical and Translational Science Research Retreat

Soil-transmitted helminths (STHs), most notably, hookworms, whipworms, and Ascaris, are nematodes that infect more than 1.5 billion of the poorest people and are amongst the leading causes of morbidity worldwide. Only two classes of de-worming drugs (anthelmintics) are available for treatment, and only one is commonly used in mass drug administrations. New anthelmintics are urgently needed to overcome emerging resistance and to produce higher cure rates. Crystal (Cry) proteins, in particular Cry5B, made by Bacillus thuringiensis (Bt) are promising new candidates. Cry5B has excellent anthelmintic properties against many free-living and parasitic nematodes, including in vivo efficacy against multiple STH ...


Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török May 2016

Theoretical And Experimental Analysis Of The Antioxidant And Anti-Amyloid Features Of Synthetic Resveratrol Mimics, William Horton, Anne Kokel, Fanni Török, Chris Tran, Marianna Török, Bela Török

UMass Center for Clinical and Translational Science Research Retreat

Diaryl hydrazones, possessing similar structure to the popular red wine antioxidant resveratrol, have been previously identified as multitarget compounds interfering with several processes associated with the pathogenesis of Alzheimer’s disease (AD). These compounds exhibited particularly strong inhibition of the amyloid beta (A) peptide self-assembly, including blocking the formation of fibrils and oligomers, species that are widely accepted to be neurotoxic. The molecules were also powerful free radical scavengers and thus have a potential to defend against oxidative stress.

In order to learn more about the mode of action of the compounds, theoretical and experimental studies have been carried out ...


Terpenes As ‘Resistance-Busting” Anthelmintic Drug, Zeynep Mirza, David Koch, Thanh-Thanh Nguyen, Yan Hu, Raffi V. Aroian, Gary R. Ostroff May 2016

Terpenes As ‘Resistance-Busting” Anthelmintic Drug, Zeynep Mirza, David Koch, Thanh-Thanh Nguyen, Yan Hu, Raffi V. Aroian, Gary R. Ostroff

UMass Center for Clinical and Translational Science Research Retreat

There is an urgent need for new therapies for parasitic helminthic diseases affecting 1.5-2 billion people worldwide due to the threat of wide-spread resistance development to existing treatments and due to problems of incomplete efficacies.

Terpenes are plant secondary metabolites and major essential oil constituents. Historically, the terpene thymol was successfully used to cure hookworm infections in the 1900’s. Although effective, large doses were needed and thymol treatment had significant side effects. Because free terpenes are absorbed in the stomach, less than 10% of oral terpenes entered the site where the parasites live. To overcome these problems we ...


Enhancing Antibiotic Activity Using Nanomaterial-Antibiotic Conjugates, H. Surangi N. Jayawardena, Thareendra De Zoysa, Kalana W. Jayawardana, Scott T. Boiko, Mingdi Yan May 2014

Enhancing Antibiotic Activity Using Nanomaterial-Antibiotic Conjugates, H. Surangi N. Jayawardena, Thareendra De Zoysa, Kalana W. Jayawardana, Scott T. Boiko, Mingdi Yan

UMass Center for Clinical and Translational Science Research Retreat

We demonstrate that streptomycin conjugated on silica nanoparticles (SNP-Str) can be used to effectively target streptomycin-resistant Escherichia coli (E. coli) bacteria by lowering the minimum inhibitory concentration (MIC) of streptomycin up to 2 log folds. Silica nanoparticles were synthesized with an average diameter of 80, 50 and 30 nm, respectively. Streptomycin was then covalently conjugated to SNP using efficient photocoupling chemistry. The MIC for free streptomycin sulfate was recorded as a high 2.0 mg/mL for an engineered Strr mutant E. coli ORN 208. Conjugating the streptomycin to SNP resulted in the decrease in MIC to 161 μg/mL ...


Interactions Of Carbohydrate-Conjugated Nanoparticles With Mycobacterium Smegmatis, Kalana W. Jayawardana, H. Surangi N. Jayawardena, Thareendra De Zoysa, Mingdi Yan May 2014

Interactions Of Carbohydrate-Conjugated Nanoparticles With Mycobacterium Smegmatis, Kalana W. Jayawardana, H. Surangi N. Jayawardena, Thareendra De Zoysa, Mingdi Yan

UMass Center for Clinical and Translational Science Research Retreat

Mycobacterium smegmatis is a non-pathogenic microorganism and has been widely used as a model organism to study infections caused by M. tuberculosis and other mycobacterial pathogens. We report that nanoparticles conjugated with selected carbohydrate show a striking increase in the surface adherence by M. smegmatis. This applies to silica nanoparticles and magnetic nanoparticles ranging from 100 nm to 5 nm. Under the same experimental conditions, minimum adhesion was observed for unfunctionalized nanoparticles. The synthesis and characterization of the glyconanoparticles will be presented. The finding is applied to imaging M. smegmatis infected lung epithelial cells, and the results will be discussed.


In Vivo Evaluation Of A Biomimetic Polymer-Doxorubicin Conjugate For Cancer Therapy, Matthew Skinner, Samantha Mcrae Page, Xiangji Chen, Sangram S. Parelkar, Kaitlyn Wong, Maria Mora, Sallie S. Schneider, Todd S. Emrick May 2014

In Vivo Evaluation Of A Biomimetic Polymer-Doxorubicin Conjugate For Cancer Therapy, Matthew Skinner, Samantha Mcrae Page, Xiangji Chen, Sangram S. Parelkar, Kaitlyn Wong, Maria Mora, Sallie S. Schneider, Todd S. Emrick

UMass Center for Clinical and Translational Science Research Retreat

This poster will describe a novel polymer pro-drug platform designed for conjugation and delivery of chemotherapeutics. Specifically, polymer pro-drugs were prepared from functional polymer zwitterions and doxorubicin (DOX), and evaluated in vivo to assess toxicological, pharmacokinetic and therapeutic properties. The biocompatible polymer scaffold (PolyMPC) consists of zwitterionic phosphorylcholine pendent groups, which mimic the natural hydrophilic moieties of phospholipids in cell membranes, and hydrazone linkages that allow for pH-triggered release of DOX. PolyMPC-DOX pro-drugs were isolated as dry solids using a facile strategy that allows for precise control of molecular weight and DOX incorporation. In vivo toxicity of PolyMPC and PolyMPC-DOX ...