Ph.D. Indiana University, 1968

Drug-Bioreceptor Interactions, Quantitative Structure-Activity Relationships and Drug Design

Interaction of drugs with nucleic acids

Among the drugs currently under investigation as potentially useful anticancer drugs and/or antiviral agents, there are many which exert their pharmacological action by direct interaction with nucleic acids. We examine the interaction of drugs with nucleic acids; investigate the structure and activity of anticancer drugs, antiviral agents, antibiotics, and interferon inducers; and study the relationship between structure and biological function. We use a variety of techniques such as molecular co-crystallization/X-ray diffraction, solution spectroscopic techniques, bioassay and computer-assisted methods. The specific aims of our research are to elucidate the mechanisms of drug-nucleic acid interactions; to obtain a more comprehensive understanding of the chemical structure requirements and molecular mechanisms of anticancer or antiviral drug action and interferon induction; and to develop a rationale for the design of more effective and less toxic drugs for the treatment of neoplastic diseases, viral infections and infectious diseases.

We are currently investigating a number of fascinating problems in biochemistry and computational chemistry such as drug-nucleic interactions, structure and activity of anticancer drugs, antiviral agents, antibiotics and interferon inducers, and structure-activity relationship studies. Some of the research projects which are under investigation include the following:

Interaction of drugs with biopolymers:

• Structural studies of drug-biopolymer complexes.
• In vitro antiviral studies of drug-biopolymer combinations.

In vitro antiviral, anticancer, antibacterial activity studies of polyphenols.

Computer-assisted molecular/drug design and quantitative structure-activity relationship (QSAR) studies:

• Structure and activity/property relationships of chemical compounds such as antiviral agents, anticancer drugs, antibiotics, interferon inducers, and liquid crystal compounds.
• Modeling chemical transformation pathways using graph-theoretic transforms and structure-reactivity maps.
• Molecular modeling using similarity-based algorithms and techniques.
• Molecular design and mixture formulation of liquid crystals.
• Correlation and prediction of aqueous solubilities of organic pollutants and related compounds.
• The development and application of computer algorithms and software using molecular topology, chemical graph theory and chemical information theory for quantitative molecular similarity analysis (QMSA) and quantitative structure-activity relationship (QSAR) studies.