Antioxidant, Antidiabetic and Anticancer Activities of L-Phenylalanine and L-Tyrosine Ester Surfactants: In Vitro and In Silico Studies of their Interactions with Macromolecules as Plausible Mode of Action for their Biological Properties

Abstract

Background: Aromatic amino acid-based surfactants have been found to have interesting biological properties such as antibacterial and hemolytic activities. Recently, we have reported the antibacterial activity of a range of ester hydrochloride surfactants derived from L-Phenylalanine and LTyrosine. This study aims at assessing the antioxidant, α-glycosidase inhibitory and cytotoxic activities of a series of L-Phenylalanine and L-Tyrosine ester hydrochlorides. Molecular docking and BSA binding studies were also carried out in order to investigate their potential therapeutic targets. Methods: L-Phenylalanine and L-Tyrosine surfactants were tested as potential lipophilic antioxidants using the DPPH and ABTS assays. These surfactants were also tested for their α-glycosidase inhibitory activity using 4-nitrophenyl α -D-glucopyranoside (pNPG) as substrate. Their cytotoxicity effects were screened using HeLa and KB cell lines. Glide version 5.7 as implemented in Schrödinger suite 2013-1, was used for performing docking studies of L-Phenylalanine and L-Tyrosine dodecyl esters. The interaction of the ester hydrochlorides of L-Phenylalanine and L-Tyrosine with bovine serum albumin (BSA) was investigated using fluorometric titration. Results: The presence of the phenolic moiety in L-Tyrosine-based surfactants was found to enhance the antioxidant and α-glucosidase inhibitory activities compared to the L-Phenylalanine derivatives. The α- glucosidase and anticancer activities of the phenylalanine surfactants were found to increase with chain length up to C12 above which the activities exhibited a downward trend. In the case of the tyrosine series, an increase in chain length from C8 to C14 was found to decrease the α-glucosidase inhibitory activity and increase the anticancer activity of the surfactants. Binding studies with bovine serum albumin showed that the tyrosine surfactants displayed greater affinity for the serum albumin, owing to the presence of the phenolic group which altered the orientation of the surfactant molecule within the hydrophobic core of BSA. Conclusion: L-Tyrosine esters having a phenolic moiety were found to possess enhanced biological activity in terms of both the antioxidant and antidiabetic activities as well as also bind more strongly to Bovine serum albumin. Molecular docking studies of the phenylalanine and tyrosine surfactants of similar chain length with target proteins showed direct correlation with their anticancer and antidiabetic activity. Therefore, the findings show that these aromatic based surfactants derived from L-Tyrosine can act as promising antioxidant, antidiabetic and anticancer agents, and they can also be efficiently transported and eliminated in the body, making them useful candidates for drug designs.

Synthesis, docking studies, in vitro cytotoxicity evaluation and DNA damage mechanism of new tyrosine‐based tripeptides

“…[ 3,7,47 ] The ability of peptides to bind to different receptors and be a part of various biochemical pathways allows them to function as potential diagnostic tools and biomarkers. [ 48–55 ]…”

“…[3,7,47] The ability of peptides to bind to different receptors and be a part of various biochemical pathways allows them to function as potential diagnostic tools and biomarkers. [48][49][50][51][52][53][54][55] Although the studies carried out in recent years have provided significant advances in the diagnosis and treatment of cancer, intensive research continues for the search for new drug candidates with increased efficacy and least side effects. [56,57] In this context, peptides and peptide conjugates in particular are of great interest because of their potential as anticancer agents.…”

Cytotoxic activities of Cyamopsis tetragonoloba L. seed extracts against huh-7 human liver cancer cells

“…As a result, increasing ROS generation needs an increase in antioxidant production (Lieu et al, 2020). According to previous studies, excessive levels of essential amino acids and polyphenols in guar seeds may be associated to anticancer properties (Tripathi andPandey, 2016, Saeed et al, 2017), due to their antioxidant activity (Joondan et al, 2019).…”

Potential Photoprotective Effect of Dietary Corn Silk Extract on Ultraviolet B-Induced Skin Damage

“…Proline and glycine betaine are antioxidants that also protect plants from dehydration [52], salt stress, and cell death [53]. L-phenylalanine exerts lipophilic antioxidant capacity as tested by DPPH and ABTS assays [54] and anti-inflammatory effects on carrageenan-induced edema [55]. Phytosphingosine, an active lipid abundant in both plants and animals, constitutes the stratum corneum (outer layer of skin) and exhibits anti-inflammatory effect and defense against microbes [56].…”