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Medicinal-Pharmaceutical Chemistry Commons™
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- Cytochrome P450; coumarins; docking; quantitative structure-activity relationship (QSAR); hologram quantitative structure-activity relationship (HQSAR); comparative molecular field analysis (CoMFA); comparative molecular similarity index analysis (CoMSIA); molecular modeling; active site; competitive inhibition; time-dependent inhibition (1)
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Articles 1 - 8 of 8
Full-Text Articles in Medicinal-Pharmaceutical Chemistry
Coumarins And P450s, Studies Reported To-Date, Maryam Foroozesh, Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu
Coumarins And P450s, Studies Reported To-Date, Maryam Foroozesh, Jayalakshmi Sridhar, Navneet Goyal, Jiawang Liu
Faculty and Staff Publications
Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in themetabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.
Transactivation Of Human Endogenous Retroviruses By Tumor Viruses And Their Functions In Virus-Associated Malignancies., Jungang Chen, Maryam Foroozesh, Zhiqiang Qin
Transactivation Of Human Endogenous Retroviruses By Tumor Viruses And Their Functions In Virus-Associated Malignancies., Jungang Chen, Maryam Foroozesh, Zhiqiang Qin
Faculty and Staff Publications
Human endogenous retroviruses (HERVs), viral-associated sequences, are normal components of the human genome and account for 8–9% of our genome. These original provirus sequences can be transactivated to produce functional products. Several reactivated HERVs have been implicated in cancers and autoimmune diseases. An emerging body of literature supports a potential role of reactivated HERVs in viral diseases, in particular viral-associated neoplasms. Demystifying studies on the mechanism(s) of HERV reactivation could provide a new framework for the development of treatment and prevention strategies targeting virus-associated tumors. Although available data suggest that coinfection by other viruses, such as Kaposi’s Sarcoma-associated herpesvirus (KSHV) …
Zb716, A Steroidal Selective Estrogen Receptor Degrader (Serd), Is Orally Efficacious In Blocking Tumor Growth In Mouse Xenograft Models., S. Guo, Changde Zhang, M. Bratton, M Mottamal, Jiawang Liu, Peng Ma, P. Ma, Shilong Zheng
Zb716, A Steroidal Selective Estrogen Receptor Degrader (Serd), Is Orally Efficacious In Blocking Tumor Growth In Mouse Xenograft Models., S. Guo, Changde Zhang, M. Bratton, M Mottamal, Jiawang Liu, Peng Ma, P. Ma, Shilong Zheng
Faculty and Staff Publications
Advances in oral SERDs development so far have been confined to nonsteroidal molecules such as those containing a cinnamic acid moiety, which are in earlystage clinical evaluation. ZB716 was previously reported as an orally bioavailable SERD structurally analogous to fulvestrant. In this study, we examined the binding details of ZB716 to the estrogen receptor alpha (ERα) by computer modeling to reveal its interactions with the ligand binding domain as a steroidal molecule. We also found that ZB716 modulates ERα-coregulator interactions in nearly identical manner to fulvestrant. The ability of ZB716 to inhibit cell growth and downregulate ER expression in endocrine …
Synthesis And Antitumor Activity Of N-Triazol-5-Yl-Oxazolidin-4-One Derivatives., R. Luo, S. Guo, Shilong Zheng, Guangdi Wang, X. Bao, L. He
Synthesis And Antitumor Activity Of N-Triazol-5-Yl-Oxazolidin-4-One Derivatives., R. Luo, S. Guo, Shilong Zheng, Guangdi Wang, X. Bao, L. He
Faculty and Staff Publications
Fifteen novel N-triazol-5-yl-oxazolidin-4-ones were synthesized through a few of steps from the benzaldehydes. It was found that N-iodosuccinimide (NIS) can promote intramolecular amination reaction which is the key step of the syntheses, which will be used as new method for the intramolecular formation of nitrogen-containing heterocycles. Part of the compounds were evaluated for their anticancer activity. Among them, compounds 6a, 6b and 6c showed moderate antiprolifiration activity toward human breast cancer cells MDA-MB-231 cell lines, while the mild activity of 6a, 6b and 6d against human cervical cancer HeLa cell lines was confirmed in vitro assay.
Ligands Of Therapeutic Utility For The Liver X Receptors., Rajesh Komati, Dominick Spadoni, Shilong Zheng, Jayalakshmi Sridhar
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. …
Copper Salt-Catalyzed Formation Of A Novel Series Of Triazole-Spirodienone Conjugates With Potent Anticancer Activity., L. Gu, P. Wang, Qiu Zhong, Y. Deng, J. Xie, F. Liu, F. Xiao, Shilong Zheng, Y. Chen, Guangdi Wang, L. He
Copper Salt-Catalyzed Formation Of A Novel Series Of Triazole-Spirodienone Conjugates With Potent Anticancer Activity., L. Gu, P. Wang, Qiu Zhong, Y. Deng, J. Xie, F. Liu, F. Xiao, Shilong Zheng, Y. Chen, Guangdi Wang, L. He
Faculty and Staff Publications
Copper salt-catalyzed oxidative amination resulted in the formation of a novel series of triazole-spirodienone conjugates, 4-triazolyl-1-oxa-4-azaspiro[4,5]deca-6,9-dien-3,8-diones and 4-triazolyl-1-oxa-4-azaspiro[4,5]deca-6,9-dien-8-ones. A single crystal of compound 1p among them was grown and analyzed by X-ray crystallography. These compounds were evaluated for their antiproliferative activities against MDA-MB-231, HeLa, A549 and MCF-7 cell lines. Most of them showed moderate to high anticancer potency in the four cancer cell lines. The discovery of the triazole-spirodienone conjugates as cytotoxic agents against cancer cells may open up a new field in which these novel small molecules could be further explored as promising anticancer agents.
Small Molecule Tyrosine Kinase Inhibitors Of Erbb2/Her2/Neu In The Treatment Of Aggressive Breast Cancer., Richard L. Schroeder, Cheryl L. Stevens, Jayalakshmi Sridhar
Small Molecule Tyrosine Kinase Inhibitors Of Erbb2/Her2/Neu In The Treatment Of Aggressive Breast Cancer., Richard L. Schroeder, Cheryl L. Stevens, Jayalakshmi Sridhar
Faculty and Staff Publications
he human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin®) and lapatinib (Tyverb/Tykerb®), a monoclonal antibody inhibitor …
Insights On Cytochrome P450 Enzymes And Inhibitors Obtained Through Qsar Studies, Jayalakshmi Sridhar, Jiawang Liu, Maryam Foroozesh, Cheryl Stevens L. Klein Stevens
Insights On Cytochrome P450 Enzymes And Inhibitors Obtained Through Qsar Studies, Jayalakshmi Sridhar, Jiawang Liu, Maryam Foroozesh, Cheryl Stevens L. Klein Stevens
Faculty and Staff Publications
The cytochrome P450 (CYP) superfamily of heme enzymes play an important role in the metabolism of a large number of endogenous and exogenous compounds, including most of the drugs currently on the market. Inhibitors of CYP enzymes have important roles in the treatment of several disease conditions such as numerous cancers and fungal infections in addition to their critical role in drug-drug interactions. Structure activity relationships (SAR), and three-dimensional quantitative structure activity relationships (3D-QSAR) represent important tools in understanding the interactions of the inhibitors with the active sites of the CYP enzymes. A comprehensive account of the QSAR studies on …