2D QSAR APPROACH TO DEVELOP NEWER GENERATION SMALL MOLECULES ACTIVE AGAINST SMALL LUNG CANCER CELL LINE DMS 114
Supriyo Saha, Prinsa, Mrityunjoy Acharya
Sardar Bhagwan Singh Post Graduate Institute of Biomedical Sciences and Research. Balawala, Dehradun, India. Ved Life Savers (P) Limited, Dehradun. Rastriya Bal Suraksha Karyakam, Howrah, West Bengal, India.
Keywords: Small Lung Cancer, PADEL, Stepwise regression, FA-MLR, Golbraikh and Tropsha acceptable model, Euclidean and Mahalanobis Distance.
Quantative Structure Activity Relationship analysis was performed using 38 small molecules without any particular scaffold worked against small lung cancer cell line DMS 114. The QSAR model was pIC50 = 32.72228(+/-9.85895) +0.16592(+/-0.11717) ALogP -0.00745(+/-0.00466) AMR -3.74232(+/-1.26299) Mi +0.3363(+/-0.03428) RDF110m. Statistical information for that equation was SEE :0.81811, r^2 :0.8621, r^2 adjusted :0.83584, F :32.82184 (DF :4, 21) which suggested that AlogP (Ghose-Crippen LogKo/w), RDF110m (Radial distribution function - 100 / weighted by relative mass) create positive response and AMR (Molar refractivity), Mi (Mean ionization potentials (scaled on carbon atom)) create negative response towards PIC50 value. Then the model was validated through Golbraikh and Tropsha acceptable model criteria's as Q^2:0.77691 Passed (Threshold value Q^2>0.5),r^2: 0.61064 Passed (Threshold value r^2>0.6, |r0^2-r'0^2|: 0.11623 Passed with Threshold value |r0^2-r'0^2|<0.3). As well as the greater q2 value was suggested the model sustainability. Applicabilty domain was identified by Euclidean and Mahalanobis Distance Method. All the points were merely overlapped with observed and predicted IC50 value. So the developed QSAR model will work as a great predictor of its activity with any chemical scaffold.