molecules-logo

Journal Browser

Journal Browser

Special Issue "A Special Issue in Honor of Prof. Duane D. Miller"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 9483

Special Issue Editor

Prof. Dr. Wei Li
E-Mail Website
Guest Editor
Professor and Director of UTHSC College of Pharmacy Drug Discovery Center, Faculty Director of Shared Analytical Instrument Facility, University of Tennessee Health Science Center, 881 Madison Avenue, room 561, Memphis, TN 38163, USA
Interests: small molecule drug discovery; chemical biology; medicinal chemistry; tubulin inhibitors; colchicine binding site inhibitors; survivin inhibitors; MDM2 inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue of Molecules is dedicated to Professor Duane D Miller, a member of the National Academy of Investors (NAI) and Professor Emeritus at College of Pharmacy, University of Tennessee Health Science Center, for his work in small molecule drug discovery and development.

Dr. Miller was born in 1943, and grew up on a farm in Larned, Kansas. He obtained his B.S. degree in Pharmacy at Kansas University in 1966, and his interest in research was stimulated by two professors at the University of Kansas, Dr. Ed Smissman and Dr. Matt Mertes. As a National Science Foundation Undergraduate Research Fellow, he worked on anticancer drugs. He next moved to Seattle, Washington, and was an NIH Fellow while at the University of Washington, where he obtained his Ph.D. in Medicinal Chemistry, in 1969, under the mentorship of Dr. Wendel L. Nelson for his research on conformationally restricted analogs of ephedrine. He next joined the Ohio State University Faculty in 1969, where he became Professor and Chairman of the Division of Medicinal Chemistry and Pharmacognosy in 1982. He had a highly synergistic collaboration with his colleagues in elucidating steric interactions of imidazolines, catecholamines, and tetrahydroisoquinolines with adrenoceptors. The classic studies provided the foundation for understanding the molecular components underlying the efficacy of agonists on adrenergic receptors. He studied dopamine and norepinephrine analogs with Drs. Popat Patil, Norman Uretsky and Dennis Feller. They were the first to discovered a set of imidazoline chiral agents that did not follow the Easson–Stedman theory (1933), which states that optically active adrenergic agonists possessing an asymmetric hydroxyl-substituted benzylic carbon atom will have the following relative potencies: R(−) > than S(+) = desoxy form of drugs binding to the adrenergic receptors. He moved to the University of Tennessee Health Science Center in Memphis, TN, in 1992, as the Van Vleet Endowed Professor of The Department of Pharmaceutical Sciences in the College of Pharmacy. He was made chair of the Department of Pharmaceutical Sciences in 2001.

Dr. Miller has published over 450 publications and 16 book chapters. He has given 343 presentations at national and international meetings and holds over 100 patents and patent applications. Dr. Miller’s research interests include the design and synthesis of new drug molecules. He has a strong interest in developing drugs for new areas in which there is currently a lack of therapeutic agents or in areas in which there is the need to develop new drugs with fewer side effects. Dr. Miller and Dr. Jim Dalton, currently Dean of the College of Pharmacy at the University of Michigan, discovered the first new nonsteroidal selective androgen receptor modulators (SARMs) and reported about them in 1998. GTx is the company that initially licensed SARMs, and has since carried out clinical studies with SARMs. These agents were studied for their use in muscle wasting and osteoporosis in cancer patients. SARMs have the advantage that they are orally active with fewer side effects, including less liver toxicity than current muscle building agents. Such agents may be of value in aging males to treat low testosterone in older males (termed ADAM (androgen decline in aging males) or also referred to as andropause). The SARMs completed Phase I, Phase II, and Phase III human clinical testing for the treatment of cachexia in cancer patients but were not approved by the FDA. Other studies are being attempted to establish a rationale for obtaining approval. Together with Dr. Ramesh Narayanan, new selective androgen receptor degraders (SARDs) were discovered that work to destroy the androgen receptor in treating castration-resistant cancer (CRPC). These latter agents are designed to help patients where regular androgen receptor antagonists have failed in prostate cancer therapy. Dr. Miller and Dr. Narayanan have also recently discovered selective androgen receptor covalent antagonists (SARCAs) that can also potentially be used for prostate cancer. He has also worked on radiation mitigators with Dr. Gabor Tigyi, and these agents are licensed to RxBio along with anti-inflammatory drugs developed with Dr. Ryan Yates. Dr. Miller has worked with Dr. Elden Geisert on drugs for the treatment of brain cancer, resulting in the development of molecules that have been licensed by RxBio.

During his academic career, Dr. Miller has been presented the University of Tennessee National Alumni Outstanding Teacher Award (1994). For teaching at the University of Tennessee Health Science Center at the College of Pharmacy, he was presented the Student Government Association Executive Council (SGAEC) Excellence in Teaching Award in 1995, 2001, and 2005. He was the UT Pharmacy Class Teacher of the Year (2006). He has mentored 29 graduate students and 35 postdoctoral researchers.

Dr. Miller was honored as an American Association Pharmaceutical Scientists (AAPS) Fellow in (1990). He was selected as an American Association for the Advancement of Science (AAAS) Fellow and honored for fundamental studies on the structural and stereochemical requirements of adrenergic drugs interacting in the CNS and peripheral nervous systems (2001). In 2008, he was recognized by the University of Washington, College of Pharmacy, as the “Alumni of the Year”. He was awarded the Division of Medicinal Chemistry Award from the American Chemical Society at the National Medicinal Chemistry Symposium in June 2008. The Division of Medicinal Chemistry Award is conferred biennually in the United States to a scientist or team of scientists with a substantial record of contributions to the field of medicinal chemistry through research, mentorship, and service to the discipline. In August 2008, he was inducted into the Medicinal Chemistry Hall of Fame of the American Chemical Society at the National American Chemical Society Meeting in Philadelphia, Pennsylvania. In 2009, he was awarded the Volwiler Research Achievement Award for research in the pharmaceutical sciences at the National American Association Colleges of Pharmacy (AACP). In 2015, he was inducted into the National Academy of Inventors at the California Institute Technology in Pasadena, California. In 2019, he was honored for being the first to have 100 US patents by the University of Tennessee Research Foundation.

In 2015, he retired and was given the title of Professor Emeritus, and he continues to conduct funded research on the design, preparation, and study of new drugs for the treatment of cancer. He is currently patenting and publishing about new drugs for prostate cancer, breast cancer, melanoma, and brain cancer (glioma) with Dr. Ramesh Narayanan, Dr. Wei Li, and Dr. Lawrence Pfeffer at the University of Tennessee Health Science Center. Dr. Wei Li and Dr. Miller have worked together for over ten years in the area of tubulin inhibitors and have developed a drug, Veu-111, that has been licensed by Veru and is currently in Phase I/II clinical trials for resistant prostate cancer in addition to entering into Phase II studies for treatment of SARS-CoV-2 respiratory distress syndrome in adults.

We are organizing a Special Issue honoring Dr. Miller’s distinguished scientific career over the past 50+ years. This Special Issue will consist of communications, original research articles, and review articles related to small molecule drug discovery and development as well as anecdotes about Dr. Duane Miller.

Prof. Dr. Wei Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2300 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (5 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

Article
Berberine, A Phytoalkaloid, Inhibits Inflammatory Response Induced by LPS through NF-Kappaβ Pathway: Possible Involvement of the IKKα
Molecules 2021, 26(16), 4733; https://doi.org/10.3390/molecules26164733 - 05 Aug 2021
Cited by 7 | Viewed by 1370
Abstract
Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) [...] Read more.
Berberine (BBR), a plant alkaloid, is known for its therapeutic properties of anticancer, cardioprotective, antidiabetic, hypolipidemic, neuroprotective, and hepatoprotective activities. The present study was to determine the molecular mechanism of BBR’s pharmacological activity in human monocytic (THP-1) cells induced by arachidonic acid (AA) or lipopolysaccharide (LPS). The effect of BBR on AA/LPS activated proinflammatory markers including TNF-α, MCP-1, IL-8 and COX-2 was measured by ELISA or quantitative real-time PCR. Furthermore, the effect of BBR on LPS-induced NF-κB translocation was determined by immunoblotting and confocal microscopy. AA/ LPS-induced TNF-α, MCP-1, IL-6, IL-8, and COX-2 markers were markedly attenuated by BBR treatment in THP-1 cells by inhibiting NF-κB translocation into the nucleus. Molecular modeling studies suggested the direct interaction of BBR to IKKα at its ligand binding site, which led to the inhibition of the LPS-induced NF-κB translocation to the nucleus. Thus, the present study demonstrated the anti-inflammatory potential of BBR via NF-κB in activated monocytes, whose interplay is key in health and in the pathophysiology of atherosclerotic development in blood vessel walls. The present study findings suggest that BBR has the potential for treating various chronic inflammatory disorders. Full article
(This article belongs to the Special Issue A Special Issue in Honor of Prof. Duane D. Miller)
Show Figures

Graphical abstract

Article
Post-Catalytic Complexes with Emtricitabine or Stavudine and HIV-1 Reverse Transcriptase Reveal New Mechanistic Insights for Nucleotide Incorporation and Drug Resistance
Molecules 2020, 25(20), 4868; https://doi.org/10.3390/molecules25204868 - 21 Oct 2020
Cited by 2 | Viewed by 1947
Abstract
Human immunodeficiency virus 1 (HIV-1) infection is a global health issue since neither a cure nor a vaccine is available. However, the highly active antiretroviral therapy (HAART) has improved the life expectancy for patients with acquired immunodeficiency syndrome (AIDS). Nucleoside reverse transcriptase inhibitors [...] Read more.
Human immunodeficiency virus 1 (HIV-1) infection is a global health issue since neither a cure nor a vaccine is available. However, the highly active antiretroviral therapy (HAART) has improved the life expectancy for patients with acquired immunodeficiency syndrome (AIDS). Nucleoside reverse transcriptase inhibitors (NRTIs) are in almost all HAART and target reverse transcriptase (RT), an essential enzyme for the virus. Even though NRTIs are highly effective, they have limitations caused by RT resistance. The main mechanisms of RT resistance to NRTIs are discrimination and excision. Understanding the molecular mechanisms for discrimination and excision are essential to develop more potent and selective NRTIs. Using protein X-ray crystallography, we determined the first crystal structure of RT in its post-catalytic state in complex with emtricitabine, (-)FTC or stavudine (d4T). Our structural studies provide the framework for understanding how RT discriminates between NRTIs and natural nucleotides, and for understanding the requirement of (-)FTC to undergo a conformation change for successful incorporation by RT. The crystal structure of RT in post-catalytic complex with d4T provides a “snapshot” for considering the possible mechanism of how RT develops resistance for d4T via excision. The findings reported herein will contribute to the development of next generation NRTIs. Full article
(This article belongs to the Special Issue A Special Issue in Honor of Prof. Duane D. Miller)
Show Figures

Figure 1

Article
Design and Synthesis of Novel Hybrid 8-Hydroxy Quinoline-Indole Derivatives as Inhibitors of Aβ Self-Aggregation and Metal Chelation-Induced Aβ Aggregation
Molecules 2020, 25(16), 3610; https://doi.org/10.3390/molecules25163610 - 08 Aug 2020
Cited by 10 | Viewed by 2073
Abstract
A series of novel hybrid 8-hydroxyquinoline-indole derivatives (7a–7e, 12a–12b and 18a–18h) were synthesized and screened for inhibitory activity against self-induced and metal-ion induced Aβ1–42 aggregation as potential treatments for Alzheimer’s disease (AD). In vitro studies identified the most inhibitory [...] Read more.
A series of novel hybrid 8-hydroxyquinoline-indole derivatives (7a–7e, 12a–12b and 18a–18h) were synthesized and screened for inhibitory activity against self-induced and metal-ion induced Aβ1–42 aggregation as potential treatments for Alzheimer’s disease (AD). In vitro studies identified the most inhibitory compounds against self-induced Aβ1–42 aggregation as 18c, 18d and 18f (EC50 = 1.72, 1.48 and 1.08 µM, respectively) compared to the known anti-amyloid drug, clioquinol (1, EC50 = 9.95 µM). The fluorescence of thioflavin T-stained amyloid formed by Aβ1–42 aggregation in the presence of Cu2+ or Zn2+ ions was also dramatically decreased by treatment with 18c, 18d and 18f. The most potent hybrid compound 18f afforded 82.3% and 88.3% inhibition, respectively, against Cu2+- induced and Zn2+- induced Aβ1–42 aggregation. Compounds 18c, 18d and 18f were shown to be effective in reducing protein aggregation in HEK-tau and SY5Y-APPSw cells. Molecular docking studies with the most active compounds performed against Aβ1–42 peptide indicated that the potent inhibitory activity of 18d and 18f were predicted to be due to hydrogen bonding interactions, π–π stacking interactions and π–cation interactions with Aβ1–42, which may inhibit both self-aggregation as well as metal ion binding to Aβ1–42 to favor the inhibition of Aβ1–42 aggregation. Full article
(This article belongs to the Special Issue A Special Issue in Honor of Prof. Duane D. Miller)
Show Figures

Graphical abstract

Review

Jump to: Research

Review
8-, 9-, and 11-Aryloxy Dimeric Aporphines and Their Pharmacological Activities
Molecules 2021, 26(15), 4521; https://doi.org/10.3390/molecules26154521 - 27 Jul 2021
Cited by 2 | Viewed by 1143
Abstract
Aporphines, a major group of aporphinoid alkaloids, exhibit interesting and diverse pharmacological activities. A set of dimeric aporphines with an aryloxy group at C8, C9, and C11 have been isolated from six genera and shown to elicit various biological activities such as antitumor, [...] Read more.
Aporphines, a major group of aporphinoid alkaloids, exhibit interesting and diverse pharmacological activities. A set of dimeric aporphines with an aryloxy group at C8, C9, and C11 have been isolated from six genera and shown to elicit various biological activities such as antitumor, antimalarial, antimicrobial, antiplatelet aggregation, antifibrotic, immunosuppressive, and vasorelaxant properties. In this review, the nomenclature, chemical structures, botanical sources, pharmacological activities, and synthetic approaches of this set of dimeric alkaloids are presented. Full article
(This article belongs to the Special Issue A Special Issue in Honor of Prof. Duane D. Miller)
Show Figures

Graphical abstract

Review
Probing Mechanisms and Therapeutic Potential of γ-Secretase in Alzheimer’s Disease
Molecules 2021, 26(2), 388; https://doi.org/10.3390/molecules26020388 - 13 Jan 2021
Cited by 7 | Viewed by 2228
Abstract
The membrane-embedded γ-secretase complex carries out hydrolysis within the lipid bilayer in proteolyzing nearly 150 different membrane protein substrates. Among these substrates, the amyloid precursor protein (APP) has been the most studied, as generation of aggregation-prone amyloid β-protein (Aβ) is a defining feature [...] Read more.
The membrane-embedded γ-secretase complex carries out hydrolysis within the lipid bilayer in proteolyzing nearly 150 different membrane protein substrates. Among these substrates, the amyloid precursor protein (APP) has been the most studied, as generation of aggregation-prone amyloid β-protein (Aβ) is a defining feature of Alzheimer’s disease (AD). Mutations in APP and in presenilin, the catalytic component of γ-secretase, cause familial AD, strong evidence for a pathogenic role of Aβ. Substrate-based chemical probes—synthetic peptides and peptidomimetics—have been critical to unraveling the complexity of γ-secretase, and small drug-like inhibitors and modulators of γ-secretase activity have been essential for exploring the potential of the protease as a therapeutic target for Alzheimer’s disease. Such chemical probes and therapeutic prototypes will be reviewed here, with concluding commentary on the future directions in the study of this biologically important protease complex and the translation of basic findings into therapeutics. Full article
(This article belongs to the Special Issue A Special Issue in Honor of Prof. Duane D. Miller)
Show Figures

Figure 1

Back to TopTop