QSAR and Drug Designing for Anti-Tumor/Anti-Cancer Activity
Journal of Analytical & Bioanalytical Techniques
Q SAR is the science which relates chemical structure of biological activity. N-arylphydroxamic acids of general formula, R 1 NOH.R 2 C=0, where R 1 and R 2 are phenyl or/and substituted phenyl groups are biomolecules as (i) They follow the "Lipinski Rule of 5", (ii) Contain both HBD and HBA sites. These molecules are neutral polyfuncitonal molecules and hydrogen-bonds helps in drug delivery system by providing binding interaction with receptors. The hydrophobic, electronic and steric
... nd steric parameters of 20 such molecules are derived following the experimental techniques along with computation methods. The antiproliferative effect of these molecules was studies in-vitro and and in-vivo. The biological parameters like concentration, time intervals and survival period are also measured. Based on these data the mechanism of death of cancerous cell is studied under the heads, (i) ROS, (ii) Mitochondrial potential (iii) Lipid peroxidation and (iv)DNA Ladder. The QSAR parameters determined are correlated with biological activity estimated, following the MRA and PLS methods and the potency of molecules are computed, by formulating and generating the equations for the molecules under study. All the molecules investigated show anti-tumor activity when tested in-vitro. One molecule, N-p-Chlorophenys-4-bromobenzohydroxamic acid with best IC 50 value (53 micro molar) is selected for in-vivo experiments. The results show that 100 mg of this molecule kills 90% cancerous cells in 16 days, per kg. wt. of mice with the clean death of cancerous cells.