Biophysical interactions, docking studies and cytotoxic potential of a novel propofol-linolenate: a multi-technique approach

Abstract

In the present study, we have analyzed the biophysical interactions of alpha-linolenic acid conjugate (2,6P-ALA) with human serum albumin (HSA) and calf thymus DNA (CT-DNA); and also determined its effect on human cancer cell lines. The results of interactions between 2,6P-ALA and HSA intrinsic fluorescence indicated static quenching of HSA by the target conjugate with overall Stern-Volmer quenching constant (K_sv) value of 1.8 × 10³ M⁻¹. At high concentrations, 2,6P-ALA caused conformational variations in HSA with evident increase in α-helices. Docking studies also revealed preferential binding of 2,6P-ALA at the hydrophobic cavity of site IB with suggestive involvement of hydrophobic forces. Likewise, the conjugate was also able to quench the fluorescence intensity of CT-DNA with static type of quenching signifying the probability of interaction between them. In case of competitive interaction with ethidium bromide (EB) bound CT-DNA also; the conjugate replaced the EB depicting intercalation to be the main type of binding force. Results of cytotoxic effect of 2,6P-ALA showed significant inhibition of cancer cells growth in a concentration-dependent manner. Conjugate was most potent on MCF-7 cells. Fluorescence microscopic image of MCF-7 cells at IC₅₀ concentration of 24 µM revealed distinct morphological changes that were characteristic of programed cell death. Overall, these results complement with the previous findings of 2,6P-ALA and provide added statistics about the prospect of their transport in blood plasma.

Communicated by Ramaswamy H. Sarma

Keywords:

• Propofol-linolenate
• HSA
• fluorescence quenching
• circular dichroism
• CT-DNA
• ethidium bromide
• molecular docking

Acknowledgment

Authors would like to extend their sincere appreciation to the Deanship of Scientific Research at King Saud University for funding of this research through the Research Group Project No. RGP-212.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the Deanship of Scientific Research at King Saud University [Research Group Project No. RGP-212].