Mahesh Lakshman Ph.D.
- BSc University of Bombay (now Mumbai)
- MSc University of Bombay (now Mumbai)
- MS University of Oklahoma
- PhD University of Oklahoma
ORGANIC SYNTHESIS AT THE CHEMISTRY BIOLOGY INTERFACE
There has been a proposal that non-planarity of polycyclic aromatic hydrocarbons may influence their DNA adduct forming abilities and the net biological effect of the DNA adducts. Therefore, our group has been interested in the synthesis of non-planar PAHs as well as their metabolic profiles and biological activities. In this context we have synthesized 1,4-dimethylbenzo[c]phenanthrene (1,4-DMBcPh) and its metabolites. This PAH is 35 degrees out of plane (Figure 4) compared to the unsubstituted benzo[c]phenanthrene (BcPh, which is 25 degrees out of plane).
Our studies have shown that 1,4-DMBcPh and its putative metabolites exhibit helical properties and the isomers undergo slow helical interconversion (Figure 5). In addition, 1,4-DMBcPh is less readily oxidized to its terminal diol epoxide metabolites by cytochrome P450 1B1 and metabolic activation in the final epoxidation step is substantially influenced by the distortion in the molecule.
- Chemistry & Biochemistry:
- Associate Professor