Cytotoxity Of Marine Algal Steroids In Hela Cells – 2d & 3d Qsar Approach

Abstract

The steroids of the brown alga Turbinaria conoides were recognized as having mild-to-moderate cytotoxicity in HeLa cell, as it is being investigated towards determination of toxicity with various drugs. The cytotoxicity in HeLa cells was expressed in terms of 50% cytotoxic concentration (CC₅₀). These oxygenated steroids exhibited cytotoxicity against HeLa cells with CC₅₀ values ranging from 60.9 µg/mL to >100 µg/mL. To analyse for their cytotoxicity, Quantitative structure activity relationship (QSAR) study was performed. It was done by multiple regression analysis with simulated annealing method of partial least square (PLS) model.

A PLS model (r² = 0.90, q² = 0.80, pred_r² = 0.96) was used as a base of consensus prediction of cytotoxicity. QSAR studies indicated the carbon atom (T_C_O_4: 12%) and any atom (T_2_2_7: 15%) away from the oxygen and double bond respectively, atomic valence connectivity index-order 0 (chiV0: 50%) and distance between most hydrophobic and hydrophilic point on the VanderWaals surface (XAMostHydrophobicHydrophilic distance: 20%) correlating well with mild cytotoxicity while the partial charges of the molecules (dipole moment: 25%) contributing moderate cytotoxicity.

The 3D QSAR model further described that less bulkier substituent is required at steric site S_2441. Thus it can be concluded from the present study that cytotoxicity can be achieved by modifying the aromatic ring and preferring less bulky group to reduce steric hindrance.