Open Access. Powered by Scholars. Published by Universities.®

Medicinal-Pharmaceutical Chemistry Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 6 of 6

Full-Text Articles in Medicinal-Pharmaceutical Chemistry

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie Jun 2017

Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie

Mahurin Honors College Capstone Experience/Thesis Projects

With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay …


Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia May 2017

Development Of Neurotensin-Based Radiopharmaceuticals For Neurotensin-Receptor-1-Positive Tumors Targeting, Yinnong Jia

Theses & Dissertations

The neurotensin receptor 1 (NTR1) is overexpressed in many cancers, due to its role as a growth pathway. These NTR1-positive cancers include pancreatic, colon, prostate and breast cancers. In the radiopharmaceutical field, the overexpression of NTR1 in cancer has prompted the development of NTR1-targeted diagnostics and therapeutics. The neurotensin (NT) peptide exhibits low nanomolar affinity for NTR1 and has been the paradigm for NTR1-targeted agents. Since the 1980’s, radiolabeled NT analogs have been developed and evaluated for targeting NTR1-positive cancers. Since native NT is rapidly degraded in vivo by a variety of peptidases, a tremendous amount of effort has been …


Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett May 2017

Synthesis And In-Vitro Cell Viability/Cytotoxicity Studies Of Novel Pyrrolobenzodiazepine Derivatives, John M. Jarrett

Undergraduate Honors Theses

Pyrrolobenzodiazepines (PBDs) are a group of naturally occurring compounds that were discovered in the cultures of Streptomyces in the 1960s. Some natural PBDs discovered in these cultures, such as anthramycin and sibiromycin, were shown to possess a broad spectrum of anti-tumor activity. Since cancer is still a leading cause of death globally, the development of novel anti-proliferative derivatives of PBDs is essential for human welfare worldwide. Further synthesis and structure-activity relationship (SAR) studies of the parent natural products and their tetracyclic analogs will lead to the discovery of drug candidates. In this work, thirteen PBD analogues were synthesized using no …


Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar Jan 2017

Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar

Faculty and Staff Publications

Liver X receptors (LXRs) have been increasingly recognized as a potential therapeutic target to treat pathological conditions ranging from vascular and metabolic diseases, neurological degeneration, to cancers that are driven by lipid metabolism. Amidst intensifying efforts to discover ligands that act through LXRs to achieve the sought-after pharmacological outcomes, several lead compounds are already being tested in clinical trials for a variety of disease interventions. While more potent and selective LXR ligands continue to emerge from screening of small molecule libraries, rational design, and empirical medicinal chemistry approaches, challenges remain in minimizing undesirable effects of LXR activation on lipid metabolism. …


Synthesis Of Vorinostat And Cholesterol Conjugate To Enhance The Cancer Cell Uptake Selectivity, Nethrie D. Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su Ph.D. Jan 2017

Synthesis Of Vorinostat And Cholesterol Conjugate To Enhance The Cancer Cell Uptake Selectivity, Nethrie D. Idippily, Chunfang Gan, Paul Orefice, Jane Peterson, Bin Su Ph.D.

Chemistry Faculty Publications

Histone deacetylase (HDAC) inhibitors modulate various cellular functions including proliferation, differentiation, and apoptosis. Vorinostat (SuberAniloHydroxamic Acid, SAHA) is the first HDAC inhibitor approved by FDA for cancer treatment. However, SAHA distributes in cancer tissue and normal tissue in similar levels. It will be ideal to selectively deliver SAHA into cancer cells. Rapidly growing cancer cells have a great need of cholesterol. Low-density lipoprotein (LDL) is the major cholesterol carrier in plasma and its uptake is mediated by LDL-receptor (LDL-R), a glycoprotein overexpressed on the surface of cancer cells. Herein, we designed and synthesized a SAHA cholesterol conjugate, and further formed …


Improving Binding Affinity Through Cyclization, Kaylee M. Newcomb, Nicolas Abrigo Jan 2017

Improving Binding Affinity Through Cyclization, Kaylee M. Newcomb, Nicolas Abrigo

Undergraduate Research Posters

Cancer chemotherapy results in systematic damage as the drugs used are also toxic to benign tissue. Sensitizing a cancer cell to therapy by interfering with the DNA repair mechanisms would decrease overall toxicity, as the necessary dosage of chemotherapy drugs would be lowered. The Hartman lab developed a peptide (8.6) that binds with a KD of 1 μM to the C-terminal domain of breast cancer associated protein (BRCA1), blocking homologous recombination. The crystal structure of the peptide shows the tyrosine and threonine residues are close together, suggesting that by cyclizing these positions, the peptide may already be constrained into its …