Generic placeholder image

Current Bioactive Compounds


ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

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

Author(s): Nausheen Joondan, Sabina J. Laulloo*, Prakashanand Caumul and Prashant S. Kharkar

Volume 15 , Issue 6 , 2019

Page: [610 - 622] Pages: 13

DOI: 10.2174/1573407214666180829125309

Price: $65


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.

Keywords: Phenylalanine, tyrosine, surfactants, antioxidant, α-glucosidase, anticancer, molecular docking.

Graphical Abstract
Bordes, R.; Holmberg, K. Amino acid-based surfactants – Do they deserve more attention? Adv. Colloid Interface Sci., 2015, 222, 79-91.
[] [PMID: 25846628]
Infante, M.R.; Peréz, L.; Pinazo, A.; Clapés, P.; Moran, M.C.; Angelet, M.; Garcia, M.T.; Vinardell, M.P. Amino acid-based surfactants. C. R. Chim., 2004, 7, 583-592.
Chandra, N.; Tyagi, V.K. Synthesis, properties, and applications of amino acids based surfactants: A review. J. Dispers. Sci. Technol., 2013, 34, 800-808.
Clapés, P.; Infante, M.R. Amino acid-based surfactants: Enzymatic synthesis, properties and potential applications. Biocatal. Biotransform., 2002, 20, 215-233.
Pinazo, A.; Pons, R.; Pérez, L.; Infante, M.R. Amino acids as raw material for biocompatible surfactants. Ind. Eng. Chem. Res., 2011, 50, 4805-4817.
Pinazo, A.; Manresa, M.A.; Marques, A.M.; Bustelo, M.; Espuny, M.J.; Pérez, L. Amino acid–based surfactants: New antimicrobial agents. Adv. Colloid Interface Sci., 2016, 228, 17-39.
[] [PMID: 26792016]
Jadhav, V.; Maiti, S.; Dasgupta, A.; Das, P.K.; Dias, R.S.; Miguel, M.G.; Lindman, B. Effect of the head-group geometry of amino acid-based cationic surfactants on interaction with plasmid DNA. Biomacromolecules, 2008, 9(7), 1852-1859.
[] [PMID: 18517250]
Lozano, N.; Perez, L.; Pons, R.; Luque-Ortega, J.R.; Fernandez-Reyes, M.; Rivas, L.; Pinazo, A. Interaction studies of diacyl glycerol arginine-based surfactants with DPPC and DMPC monolayers, relation with antimicrobial activity. Colloids Surf. A Physicochem. Eng. Asp., 2008, 319, 196-203.
Ghosh, S.; Dey, J. Binding of fatty acid-amphiphiles to bovine serum albumin: Role of amide hydrogen bonding. J. Colloid Interface Sci., 2015, 458, 284-292.
[] [PMID: 26245717]
Sellami, M.; Chaari, A.; Aissa, I.; Bouaziz, M.; Gargouri, Y.; Miled, N. Newly synthesized dopamine ester derivatives and assessment of their antioxidant, antimicrobial and hemolytic activies. Process Biochem., 2013, 48, 1481-1487.
Kimura, Y.; Kanatani, H.; Shima, M.; Adachi, S.; Matsuno, R. Anti-oxidant activity of acyl ascorbates in intestinal epithelial cells. Biotechnol. Lett., 2003, 25(20), 1723-1727.
[] [PMID: 14626415]
Lukac, M.; Lacko, I.; Bukovsky, M.; Kyselova, Z.; Karlovsta, J.; Horvath, B.; Devinsky, F. Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine. Cent. Eur. J. Chem., 2010, 8, 194-201.
Joondan, N.; Caumul, P.; Akerman, M.; Jhaumeer-Laulloo, S. Synthesis, micellisation and interaction of novel quaternary ammonium compounds derived from l-Phenylalanine with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine as model membrane in relation to their antibacterial activity, and their selectivity over human red blood cells. Bioorg. Chem., 2015, 58, 117-129.
[] [PMID: 25618736]
Joondan, N.; Jhaumeer Laulloo, S.; Caumul, P.; Marie, D.E.P.; Roy, P.; Hosten, E. Synthesis, physicochemical properties and membrane interactions of novel quaternary ammonium surfactants derived from L-Tyrosine and L-DOPA in relation to their antimicrobial, hemolytic activities and in vitro cytotoxicity. Colloids Surf. A Physicochem. Eng. Asp., 2016, 511, 120-134.
Joondan, N.; Jhaumeer Laulloo, S.; Caumul, P. Effect of chain length on the micellisation, antibacterial, DPPC interaction and antioxidant activities of L-3,4-Dihydroxyphenylalanine (L-DOPA) esters. J. Surfactants Deterg., 2015, 18, 1095-1104.
Joondan, N.; Jhaumeer-Laulloo, S.; Caumul, P. A study of the antibacterial activity of L-phenylalanine and L-tyrosine esters in relation to their CMCs and their interactions with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, DPPC as model membrane. Microbiol. Res., 2014, 169(9-10), 675-685.
[] [PMID: 24667307]
Bernini, R.; Crisante, F.; Barontini, M.; Tofani, D.; Balducci, V.; Gambacorta, A. Synthesis and structure/antioxidant activity relationship of novel catecholic antioxidant structural analogues to hydroxytyrosol and its lipophilic esters. J. Agric. Food Chem., 2012, 60(30), 7408-7416.
[] [PMID: 22780104]
Laguerre, M.; López Giraldo, L.J.; Lecomte, J.; Figueroa-Espinoza, M.C.; Baréa, B.; Weiss, J.; Decker, E.A.; Villeneuve, P. Relationship between hydrophobicity and antioxidant ability of “phenolipids” in emulsion: a parabolic effect of the chain length of rosmarinate esters. J. Agric. Food Chem., 2010, 58(5), 2869-2876.
[] [PMID: 20131842]
Balgavý, P.; Devínsky, F. Cut-off effects in biological activities of surfactants. Adv. Colloid Interface Sci., 1996, 66, 23-63.
[] [PMID: 8857708]
Janoff, A.S.; Pringle, M.J.; Miller, K.W. Correlation of general anesthetic potency with solubility in membranes. Biochim. Biophys. Acta, 1981, 649(1), 125-128.
[] [PMID: 7306543]
Oboh, G.; Isaac, A.T.; Akinyemi, A.J.; Ajani, R.A. Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside induced lipid peroxidation in rats’ pancreas by phenolic extracts of avocado pear leaves and fruit. Int. J. Biomed. Sci., 2014, 10(3), 208-216.
[PMID: 25324703]
Honore, S.; Pasquier, E.; Braguer, D. Understanding microtubule dynamics for improved cancer therapy. Cell. Mol. Life Sci., 2005, 62(24), 3039-3056.
[] [PMID: 16314924]
El Sayed, M.; Voronkov, A.; Ogungbe, I.V.; El Hallouty, S.M.; Ahmed, K.M.; Vladimir, B.; Balaki, K. Anti-Cancer, molecular docking and structure activity relationship studies of some novel synthetic spiroindolo[3,2-b]Carbazoles as predicted HER2 and BrK kinase inhibitors. Curr. Bioact. Compd., 2018, 14, 119-133.
Seo, Y.H. Small molecule inhibitors to disrupt protein-protein interactions of heat shock protein 90 chaperone machinery. J. Cancer Prev., 2015, 20(1), 5-11.
[] [PMID: 25853099]
Malami, I.; Abdul, A.B.; Abdullah, R.; Bt Kassim, N.K.; Waziri, P.; Christopher Etti, I. In silico discovery of potential uridine-cytidine kinase 2 inhibitors from the rhizome of Alpinia mutica. Molecules, 2016, 21(4), 417.
[] [PMID: 27070566]
Colicelli, J. ABL tyrosine kinases: Evolution of function, regulation, and specificity. Sci. Signal., 2010, 3(139), re6.
[] [PMID: 20841568]
Lapenna, S.; Giordano, A. Cell cycle kinases as therapeutic targets for cancer. Nat. Rev. Drug Discov., 2009, 8(7), 547-566.
[] [PMID: 19568282]
Wilcox, G. Insulin and insulin resistance. Clin. Biochem. Rev., 2005, 26(2), 19-39.
[PMID: 16278749]
Galic, S.; Hauser, C.; Kahn, B.B.; Haj, F.G.; Neel, B.G.; Tonks, N.K.; Tiganis, T. Coordinated regulation of insulin signaling by the protein tyrosine phosphatases PTP1B and TCPTP. Mol. Cell. Biol., 2005, 25(2), 819-829.
[] [PMID: 15632081]
Wang, Y.; Jiang, X.; Zhou, L.; Yang, L.; Xia, G.; Chen, Z.; Duan, M. Synthesis and binding with BSA of a new gemini surfactant. Colloids Surf. A Physicochem. Eng. Asp., 2013, 436, 1159-1169.
Mir, M.A.; Khan, J.M.; Khan, R.H.; Rather, G.M.; Dar, A.A. Effect of spacer length of alkanediyl-alpha,omega-bis(dimethylcetylammonium bromide) gemini homologues on the interfacial and physicochemical properties of BSA. Colloids Surf. B Biointerfaces, 2010, 77(1), 54-59.
[] [PMID: 20116217]
Bolel, P.; Mahapatra, N.; Halder, M. Optical spectroscopic exploration of binding of Cochineal Red A with two homologous serum albumins. J. Agric. Food Chem., 2012, 60(14), 3727-3734.
[] [PMID: 22397587]
Wu, Q.; Jiang, F.L.; Li, C.H.; Hu, Y.J.; Liu, Y. Interaction of caffeine with bovine serum albumin: Determination of binding constants and the binding site by spectroscopic methods. Chin. J. Chem., 2011, 29, 433-440.
Zhang, H.M.; Fei, Z.H.; Tang, B.P.; Chen, J.; Tao, W.H.; Wang, Y.Q. The interaction of blood proteins with brucine. Mol. Biol. Rep., 2012, 39(4), 4937-4947.
[] [PMID: 22160569]
Peng, M.; Shi, S.; Zhang, Y. The influence of Cd2+, Hg2+ and Pb2+ on taxifolin binding to bovine serum albumin by spectroscopic methods: With the viewpoint of toxic ions/drug interference. Environ. Toxicol. Pharmacol., 2012, 33(2), 327-333.
[] [PMID: 22301163]
Li, D.; Zhu, M.; Xu, C.; Ji, B. Characterization of the baicalein-bovine serum albumin complex without or with Cu2+ or Fe3+ by spectroscopic approaches. Eur. J. Med. Chem., 2011, 46(2), 588-599.
[] [PMID: 21195512]
Bian, H.D.; Peng, X.L.; Huang, F.P.; Yao, D.; Yu, Q.; Liang, H. The spectroscopy study of the binding of an active ingredient of Dioscorea species with bovine serum albumin with or without Co(2+) or Zn(2+). Evid. Based Complement. Alternat. Med., 2014.2014247595
[] [PMID: 24991225]
Vijay, R.; Singh, J.; Baskar, G.; Ranganathan, R. Amphiphilic lauryl ester derivatives from aromatic amino acids: Significance of chemical architecture in aqueous aggregation properties. J. Phys. Chem. B, 2009, 113(42), 13959-13970.
[] [PMID: 19778004]
Beedessee, G.; Ramanjooloo, A.; Aubert, G.; Eloy, L.; Surnam-Boodhun, R.; Soest, R.W.M.V.; Cresteil, T.; Marie, D.E.P. Cytotoxic activities of hexane, ethyl acetate and butanol extracts of marine sponges from Mauritian Waters on human cancer cell lines. Environ. Toxicol. Pharmacol., 2012, 34(2), 397-408.
[] [PMID: 22743579]
Schrödinger. Small-Molecule Drug Discovery Suite Release 2013-1. Available from Schrödinger; , LLC, New York, NY,. 2013.
Friesner, R.A.; Murphy, R.B.; Repasky, M.P.; Frye, L.L.; Greenwood, J.R.; Halgren, T.A.; Sanschagrin, P.C.; Mainz, D.T. Extra precision glide: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem., 2006, 49(21), 6177-6196.
[] [PMID: 17034125]
Halgren, T.A.; Murphy, R.B.; Friesner, R.A.; Beard, H.S.; Frye, L.L.; Pollard, W.T.; Banks, J.L. Glide: A new approach for rapid, accurate docking and scoring. 2. Enrichment factors in database screening. J. Med. Chem., 2004, 47(7), 1750-1759.
[] [PMID: 15027866]
Friesner, R.A.; Banks, J.L.; Murphy, R.B.; Halgren, T.A.; Klicic, J.J.; Mainz, D.T.; Repasky, M.P.; Knoll, E.H.; Shelley, M.; Perry, J.K.; Shaw, D.E.; Francis, P.; Shenkin, P.S. Glide: A new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J. Med. Chem., 2004, 47(7), 1739-1749.
[] [PMID: 15027865]
Liu, X.; Ouyang, S.; Yu, B.; Liu, Y.; Huang, K.; Gong, J.; Zheng, S.; Li, Z.; Li, H.; Jiang, H. PharmMapper server: A web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res., , 2010, 38((Web Server issue)), W609-14.
[] [PMID: 20430828]
Berman, H.M.J.; Westbrook, J.; Feng, Z.; Gilliland, G.; Bhat, T.N.; Weissig, H.; Shindyalov, I.N.; Bourne, P.E. The protein data bank. Nucleic Acids Res., 2000, 28(1), 235-242.
[] [PMID: 10592235]
Release, S. 2013-1: Maestro, version 9.4; Schrödinger, LLC: New York, NY, 2013.

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy