Abstract
New cytotoxic steroidal glycoside of methanol extract from Kochia prostrata (L.) Schrad was investigated in this study. Bio-guided isolation from ethylacetate fraction of whole plant afforded steroidal glycosides named as 5-ene-dimethylcholest3 0 D glucoside (Kochioside 1A(1)), 5-ene-methylcholest-3-O-beta-D-glucoside (Kochioside 2A(1)) and 4-ene-dimethylcholest3-O-beta-D-glucoside (Kochioside 3A(1)). Their structures were assigned by physical and spectroscopic methods. Kochiosides 1A(1)-3A(1) showed inhibitory potential against brine shrimp lethality bioassay with etoposide standard drug. The new steroidal glycoside kochiosides 1A(1)-3A(1) showed inhibition values of 8.3201, 8.8205 and 8.2310 pg/mL, respectively with LD 50 compared to standard etoposide LD50 (7.4625 mu g/mL) drug. Moreover, six new derivatives were designed by substituting the -NH2 and -OCH3 at R1, R2 and R3 positions in the isolated compounds. Herein, various molecular descriptors, frontier molecular orbitals (FMO), electron affinity, ionization potential and molecular electrostatic potential (MEP) were carried out to understand the active sites and biological active nature of the new cytotoxic steroidal glycoside kochiosides. The effect of electron donating groups (-NH2 and -OCH3) was also investigated on the structural parameters and electronic properties in gas and solvent (DMSO) phases. The energy gap, MEP and reactivity descriptors values demonstrate that the kochioside 3A(1) retains good reactivity, which is in good agreement with current experimental studies.