Research
1. Pyrrole Imidazole
Alkaloid Derivatives to Control Biofilm Formation.
We are investigating the
effects that simple structural motifs that are embedded in
complex marine natural products have upon biofilm
development and maintenance. We have demonstrated that
simple derivatives of the natural products bromageliferin
and oroidin will inhibit and disperse biofilms from
pathogenic bacteria as well
as fungi, and mixed species biofilms. We have also
established that our 2-aminoimidazole-derived anti-biofilm
agents are non-toxic to red blood cells, mammalian cell
lines, and model organisms. The mechanistic basis by which
these compounds inhibit and disperse biofilms as well as
the effect these compounds have in vivo are being pursued. We are also interested
in developing synthetic approaches to access any predefined
substitution pattern on the 2-aminoimidazole
scaffold.
2. Small Molecule
Control of Antibiotic Resistance. We have recently discovered that a
certain sub-set of our 2-aminoimidazole library are able to
both to inhibit/disperse microbial biofilms and render
multi-drug resistant bacterial strains (MDR) susceptible to
conventional antibiotics. We are currently probing the
mechanistic basis of this activity, augmenting activity
through analogue synthesis, and exploring the
in vivo
potential of these compounds
in animal and plant models of infection.
3. Indole
Signaling. Indole is
one of the putative universal signals for bacteria,
controlling bacterial behavior such as biofilm formation,
virulence production, and acid tolerance. We are currently
developing probes of indole signaling based upon the
flustramine class of natural products and employing these
small molecules to probe multi-species interactions within
a biofilm and to further deconvolute the basis of indole
signaling across Gram-positive and Gram-negative bacteria.
4. Multi-Valent Gold
Nanoparticles for Biomedical Applications.
In collaboration with the
Feldheim group, Margolis group, and Ackerson group we are
exploring the use of multi-valent gold particles for
various biomedical appliations. We have demonstrated that
we can fabricate particles that will efficiently inhibit
HIV-1 infection and are exploring the possibility of using
these particles against HIV mutants that are resistant to
current anti-HIV therapies. We are also exploring the use
of gold nanoparticles as a combinatorial platform for the
discovery of novel antibiotics as well as a carrier for
delivering drugs across the blood/brain barrier. Recently,
we have been investigating the ability to trigger chemical
reactions on the gold nanoparticle surface and harness the
resulting reactive intermediates for biomedical
applications.
5. Medicinal
Chemistry. Our group
is also involved in various small molecule synthesis
projects that seek to optimize the activity of lead
scaffolds that are identified through screening efforts.
Currently, we are working in collaboration with the Wu and
Chen groups at the University of Alabama to develop highly
active small molecules that selectively inhibit the
RANKL-induced formation of osteoclasts for various bone
desorption diseases. We are also involved in optimizing
lead compounds for anti-AGE formation with the Basaraba lab
at Colorado State University.