In silico assay development for screening of tetracyclic triterpenoids as anticancer agents against human breast cancer cell line MCF7.

Experimental activity of a compound on cancer cell line/target is mostly analyzed in the form of percentage inhibition at different concentration gradient and time of incubation. In this study a statistical model has been developed referred as in silico assay using support vector regression model, which can act with change in concentration gradient and time of incubation. This model is a function of concentration gradient, treatment hour and independent components; which calculate the percentage inhibition in combination of above three components. This model is designed to screen tetracyclic triterpenoids active against human breast cancer cell line MCF7. The model has been statistically validated, checked for applicability domain and predicted results were reconfirmed by MTT assay, for example Oenotheranstrol derivatives, OenA & B. Computational SAR, target and docking studies were performed to understand the cytotoxic mechanism of action of Oenotheranstrol compounds. The proposed in silico assay model will work for specific chemical family for which it will be optimized. This model can be used to analyze growth kinetics pattern on different human cancer cell lines for designed compounds

Graph A (for OenA) and B (for OenB) showing concentration gradient wise variation in percentage inhibition.

<p>Graph A (for OenA) and B (for OenB) showing concentration gradient wise variation in percentage inhibition.</p

10×10 cross validation for evaluation of unbiased nature of dataset used for <i>in silico</i> assay development.

<p>10×10 cross validation for evaluation of unbiased nature of dataset used for <i>in silico</i> assay development.</p

Comparison of efficiency of kernel functions for regression modeling with given dataset.

<p>Comparison of efficiency of kernel functions for regression modeling with given dataset.</p

MetaDrug based putative target identification for exploring inhibitory activity of tetracyclic triterpenoid on MCF7 cancer cell line.

<p>System biology network (<a href="http://stitch.embl.de/" target="_blank">http://stitch.embl.de/</a>) has been drawn for OenA & B based similar compounds.</p

Graph between percentage viability & compound treatment at 24, 48, 72 & 96 hours based on MTT assay (with MCF7 cancer cell line).

<p>Graph between percentage viability & compound treatment at 24, 48, 72 & 96 hours based on MTT assay (with MCF7 cancer cell line).</p

Details about <i>in silico</i> assay model vs. experimental validation.

<p>Details about <i>in silico</i> assay model vs. experimental validation.</p

Graph A (for OenA) and B (for OenB) showing time gradient wise variation in percentage inhibition.

<p>Graph A (for OenA) and B (for OenB) showing time gradient wise variation in percentage inhibition.</p

Representation of SAR for anti-MCF7 activity defined on the basis of inhibitors used in assay model building.

<p>Representation of SAR for anti-MCF7 activity defined on the basis of inhibitors used in assay model building.</p