Quantum chemical, experimental exploration of biological activity and inhibitory potential of new cytotoxic kochiosides fromKochia prostrata(L.) Schrad

Abstract

New cytotoxic steroidal glycoside of methanol extract from Kochia prostrata ([Formula: see text]) Schrad was investigated in this study. Bio-guided isolation from ethylacetate fraction of whole plant afforded steroidal glycosides named as 5-ene-dimethylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 1A1), 5-ene-methylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 2A1) and 4-ene-dimethylcholest3-O-[Formula: see text]-D-glucoside (Kochioside 3A1). Their structures were assigned by physical and spectroscopic methods. Kochiosides 1A1–3A1showed inhibitory potential against brine shrimp lethality bioassay with etoposide standard drug. The new steroidal glycoside kochiosides 1A1–3A1showed inhibition values of 8.3201, 8.8205 and 8.2310[Formula: see text][Formula: see text]g/mL, respectively with [Formula: see text] compared to standard etoposide [Formula: see text] (7.4625[Formula: see text][Formula: see text]g/mL) drug. Moreover, six new derivatives were designed by substituting the –NH2and –OCH3at 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 (–NH2and –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 3A1retains good reactivity, which is in good agreement with current experimental studies.