Home > People > Graduate Faculty

 

 

Dr. Duy H. Hua

 

University Distinguished Professor of Chemistry

Adjunct Professor, KSU Center on Aging

B.S., Kyoto University, (1976)
Ph.D., Southern Illinois University of Carbondale, (1979)
Postdoctoral fellow, Harvard University (1980 - 1982)

Email: duy@ksu.edu
Office Phone: 785-532-6699
Lab Phone: 785-532-6664
Fax: 785-532-6666

Hua Group
News

 

Research Overview

Our research group is focusing on three major research areas, and they are: (i) Design, synthesis and evaluation of bioactive natural products and small molecules; (ii) Design, synthesis and application of beltenes and nanotubes; and (iii) Lipid derived biopolymers.

Natural product synthesis constitutes a challenging field in organic chemistry.  Our goals are to develop novel biologically active lead compounds for the development of drug candidates through the synthesis and bioevaluaiton of natural products and their simplified structures.  A number of biologically active small molecules were discovered by our collaborators and my research group. 

(1) Tricyclic pyrones were developed through the studies of the total synthesis of pyripyropene A.  This class of compounds, such as CP2, protects neuron cell death from intracellular induced amyloid beta peptides and extracellularly applied oligomeric amyloid beta peptides [1-5].  Moreover, CP2 and its analogs prevent aggregation and cholesterol accumulation in neurons expressing mutant huntingtin protein.  Surface plasmon resonance, atomic force microscopy, circular dichroism, multi-dimensional NMR spectroscopy, and protein quantification are used to study amyloid beta peptide oligomerization and disaggregation of oligomers from CP2 and its analogs.  Results suggest that CP2 and its analogs may serve as lead compounds for the development of drugs for Alzheimer and Huntington’s diseases.

We have also found that pyridine containing tricyclic pyrones, such as 3-(3-pyridyl)-1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran (3-Pyr-TP), are cytotoxic to tumor cells with IC50 values in the nanomolar to micromolar ranges [6].  The tricyclic and tetracyclic pyrones were synthesized from a one-pot condensation of 4-hydroxypyrones with various cyclic enals [7].

A new class of aldose reductase inhibitors, such as {1H,7H-5a,6,8,9-tetrahydro-1-oxopyrano[4,3-b][1]benzopyran-3-yl}acetic acid, effectively prevents the development of cataracts and diabetic retinopathy in animal models in low concentrations [8,9].

(2) During the study of the total synthesis of (+)-chloropuupehenone, we found a readily available synthetic intermediate, 8-epichloropuupehenol, inhibits lymphatic and intestinal absorption of cholesterol in vivo [10].

(3) Our research group has also embarked onto the total synthesis of ovalicin and its analogs for finding small molecules against Trypanosoma brucei parasite and inhibiting methionine aminopeptidase-2.  Our synthetic intermediates inhibit the growth of Trypanosoma brucei in nanomolar ranges, which may be used as lead compounds for the discovery of drugs to treat sleeping sickness.

(4) We are currently pursuing the total synthesis of (+)-myriceric acid A and working on the development of potent endothelin receptor antagonists for the prevention and treatment of various diseases including pulmonary arterial hypertention, control of renal function, vascular disorders, bronchopulmonary disorders, and gastronin-testinal disorders.

Molecular machines, cyclacenes, and carbon nanotubes are fascinating and synthetically challenging subjects.  Self-assembled nanotubes and molecular machines derived from substituted beltenes and cyclacenes containing a wide range of structural and functional capabilities will improve our fundamental understanding of non-covalent interactions, and provide new applications in chemical, biological and materials sciences.  Our group has been working on these synthetically challenging molecules for the past years.  It is interested to note that during our synthetic endeavor, a number of triptycene bisquinones and 1,4-anthraquinones were found to possess potent antitumor activities [11-15].

 

Selected Publications

1. Combining the rapid MTT formazan exocytosis assay and the MC65 protection assay led to the discovery of carbazole analogs as small molecule inhibitors of Ab oligomer-induced cytotoxicity.  Hyun-Seok Hong, Izumi Maezawa, Nianhuan Yao, Ruben Diaz-Avalos, Sandeep Rana, Duy H. Hua, R. Holland Cheng, Kit S. Lam, and Lee-Way Jin.  Brain Research, 2007, 1130, 223-234.

2. The relationship between S-adenosylhomocysteine hydrolase inhibitory activity and hypocholesterolemic activity of D-eritadenine.  Taro Yamada, Junichi Komoto, Kaiyan Lou, Akiharu Ueki, Duy H. Hua, Mikio Sugiyama, and Fusao Takusagawa. Biochem. Pharmacology, 2007, 73, 981-989.

3. Antitumor triptycene analogs directly interact with isolated mitochondria to rapidly trigger markers of permeability transition.  Elisabeth M. Perchellet, Yang Wang, Kaiyan Lou, Huiping Zhao, Srinivas K. Battina, Duy H. Hua, and Jean-Pierre H. Perchellet.  Anticancer Research, International Journal of Cancer Research and Treatment, 2007, 27(5), 3259-3272.

4. Novel substituted 1,4-anthracenediones with antitumor activity directly induce permeability transition in isolated mitochondria.  Elisabeth M. Perchellet, Yang Wang, Kaiyan Lou, Huiping Zhao, Duy H. Hua, and Jean-Pierre H. Perchellet.  International J. Oncology, 2007, 31, 1231-1241.

5. Combination of nanogel polyethylene glycol-polyethlenimine and 6-(hydroxymethyl)-1,4-anthracenedione as an anticancer nanomedicine.  Chanran Ganta, Aibin Shi, Srinivas K. Battina, Marla Pyle, Sandeep Rana, Duy H. Hua, Masaaki Tamura, and Deryl Troyer.  J. Nanoscience and Nanotechnology, 2008, 8(5), 2334-2340.

6. Total syntheses of (±)-ovalicin, C4(S*)-isomer, and its C5-analogs and anti-trypanosomal activities.  Duy H. Hua, Huiping Zhao, Srinivas K. Battina, Kaiyan Lou, Ana L. Jimenez, John Desper, Elisabeth M. Perchellet, Jean-Pierre H. Perchellet, and Peter K. Chiang.  Bioorg. & Med. Chem.,2008, 16, 5232-5246.

7. Synthesis and Bioevaluation of Substituted Quinolines.  Aibin Shi, Thu A. Nguyen, Srinivas Battina, Sandeep Rana, Dolores J. Takemoto, Peter K. Chiang, and Duy H. Hua.  Bioorg. & Med. Chem. Lett. 2008, 18, 3364-3368.

8. Syntheses and Properties of Cross-linked Polymers from Functionalized Triglycerides.  Hui-Ping Zhao, Jian-Feng Zhang, Xiuzhi Susan Sun, and Duy H. Hua.  Journal of Applied Polymer Science, 2008, 110, 647-656.

9. Synthesis, molecular targets, and antitumor activities of substituted tetrahydro-1-oxopyrano[4,3-b][1]benzopyrans and nanogels for drug delivery.  Elisabeth M. Perchellet, Jean-Pierre H. Perchellet, Chanran K. Ganta, Deryl L. Troyer, Aibin Shi, and Duy H. Hua.  Anti-Cancer Agents in Medicinal Chemistry, 2008, in press.

10. Protection of Retinal Cells from Ischemia by a Novel Gap Junction Inhibitor.  Satyabrata Das, Dingbo Lin, Snehalata Jena, Aibin Shi, Srinivas Battina, Duy H. Hua, Rachel Allbuagh, and Dolores J. Takemoto.  Biochemical & Biophysical Research Communications, 2008, 373, 504-508.

11. Candiate anti-Ab fluorene compounds selected from analogs of amyloid imaging agents.  Hyun-Seok Hong, Izumi Maezawa, Madhu Budamagunta, Sandeep Rana, Aibin Shi, Robert Vassar, Ruiwu Liu, Kit S. Lam, R. Holland Cheng, Duy H. Hua, John C. Voss, and Lee-Way Jin.  Neurobiology of Aging 2008, in press.  

publications continued....