Adaickapillai Mahendran

Our group’s research interest folds into two areas: a) Developing novel histone deacetylase 6 (HDAC6) selective enzyme inhibitors for cancer treatment and b) Understanding the chemistry, biological effects, and toxicity profile of oxidation products of phytocannabinoids.

Development of novel HDAC6 selective inhibitors:

HDAC6 has been identified as a potential target for cancer therapy. Current FDA-approved HDAC inhibitors, including suberoylanilide hydroxamic acid (SAHA), Panobinostat, and Belinostat contain hydroxamic acid functionality to chelate co-enzyme Zn2+ ion. Strong chelation of this hydroxamate group leads these drugs to be non-selective and toxic. Thiohydroxamic acid is a compound similar to hydroxamic acid, but its chelation properties and selectivity profiles are not fully explored. In our lab, we synthesize, characterize, and study the metal binding properties of model thiohydroxamic acid molecules. Then we study its bioactivity against HDAC enzymes and its selectivity profile with collaboration. Our long-term goal is to develop novel HDAC6 selective inhibitors (eg.  thio-HPOB) similar to known compounds HPOP and HPB.

Oxidation of phytocannabinoids and its biological effects:

Phytocannabinoids, including delta-9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD), are well known for their medicinal uses. It is also known that with prolonged exposure of these cannabinoids to sunlight, they lose their properties as they get oxidized. Cannabidiolquinone (CBDQ) is one such oxidized compound inclined to undergo further reactions with nucleophiles. It is not fully understood the biological effects of these quinone intermediates and their addition products. We are interested in the chemical oxidation process of phytocannabinoids, specifically THC and CBD. We are also interested in the mechanism of this oxidation process, supported by DFT calculations. With our biology collaborators, we study their bioactivity against different enzymes and cell-lines.