Synthesis, Characterization and In Vitro Anti-cancer  Properties of Cationic Gemini Surfactants with Alkyl Chains in Human Breast Cancer

Anwar Shalan F. ^1*, Samah Hussein Kadhim ¹

Anti-cancer activity of Gemini surfactants in human breast cancer cells

Abstract

Gemini surfactants have unique advantages in various industries such as detergents, cosmetics, paints, and pharmaceuticals due to their versatile hydrophilic-lipophilic balance. Three novel cationic surfactants, derived from alkyl alcohol and epichlorohydrin, featuring multi-alkyl multiple quaternary-ammonium salts, were synthesized with the order of C4 > C6 > C8 alkyl groups. The structure of the synthetic compounds was determined using FTIR and 1H-NMR analysis. The anti-cancer properties of the Gemini surfactants were determined with the MCF-7 breast cancer cell line, using the MTT cytotoxicity assay. We found an increase in alkyl groups (C4 > C6 > C8), indicating that larger alkyl groups contribute to improved surface qualities. The compounds showed improved surface qualities and reduced critical micelle concentration (CMC). In addition, The results showed the significant anti-cancer potential of compound B1 on the breast cancer cell line. In comparison to compounds B2 and B3, the highest inhibition was observed at concentrations from 25 to 400 µg/mL, demonstrating 26.8% to 4.3% and 32% to 4.7%, inhibition, respectively.

Keywords: Gemini surfactants, Hydrophilic-lipophilic, Cationic surfactants, Breast cancer, Anti-cancer

References

A. Bhattarai, M.A. Rub, M. Posa, B. Saha, A.M. Asiri, D. Kumar, (2022). Studies of ninhydrin and phenylalanine in cationic dimeric Gemini micellar system: Spectrophotometric and conductometric measurements, Colloids Surfaces A Physicochem. Eng. Asp. 655 (2022) 130334.

A. El Khetabi, R. Lahlali, L. Askarne, S. Ezrari, L. El Ghadaroui, A. Tahiri, J. Hrustic, S. Amiri, (2020). Efficacy assessment of pomegranate peel aqueous extract for brown rot (Monilinia spp.) disease control, Physiol. Mol. Plant Pathol. 110 (2020) 101482.

A. Setyawati, T.D. Wahyuningsih, B. Purwono, (2017). Synthesis and characterization of novel benzohydrazide as potential antibacterial agents from natural product vanillin and wintergreen oil, in: AIP Conf. Proc., AIP Publishing, 2017.

A. Shadloo, K. Peyvandi, A. Shojaeian, (2022). How the CMC adjust the liquid mixture density and viscosity of non-ionic surfactants at various temperatures?, J. Mol. Liq. 347 (2022) 117971.

A.R. Ahmady, P. Hosseinzadeh, A. Solouk, S. Akbari, A.M. Szulc, B.E. Brycki, (2022). Cationic gemini surfactant properties, its potential as a promising bioapplication candidate, and strategies for improving its biocompatibility: A review, Adv. Colloid Interface Sci. 299 (2022) 102581. https://doi.org/10.1016/j.cis.2021.102581.

A.Z. Naqvi, M. Panda, (2021). Mixed micellization: Improved physicochemical behavior of different amphiphiles in presence of gemini surfactants, J. Mol. Liq. 343 (2021) 116876.

B. Brycki, A. Szulc, (2021). Gemini surfactants as corrosion inhibitors. A review, J. Mol. Liq. 344 (2021) 117686. https://doi.org/10.1016/j.molliq.2021.117686.

B. Brycki, A. Szulc, H. Koenig, I. Kowalczyk, T. Pospieszny, S. Górka, (2019). Effect of the alkyl chain length on micelle formation for bis (N-alkyl-N, N-dimethylethylammonium) ether dibromides, Comptes Rendus Chim. 22 (2019) 386–392. https://doi.org/10.1016/j.crci.2019.04.002.

C.S. Buettner, A. Cognigni, C. Schroeder, K. Bica-Schröder, (2022). Surface-active ionic liquids: A review, J. Mol. Liq. 347 (2022) 118160.

D. Han, J. Mao, J. Zhao, H. Zhang, D. Wang, H. Cao, X. Yang, C. Lin, Y. Zhang, (2022). Dissipative particle dynamics simulation and experimental analysis of effects of Gemini surfactants with different spacer lengths on stability of emulsion systems, Colloids Surfaces A Physicochem. Eng. Asp. 655 (2022) 130205.

E. Forsyth, D.A. Paterson, E. Cruickshank, G.J. Strachan, E. Gorecka, R. Walker, J.M.D. Storey, C.T. Imrie, (2020). Liquid crystal dimers and the twist-bend nematic phase: On the role of spacers and terminal alkyl chains, J. Mol. Liq. 320 (2020) 114391. https://doi.org/10.1016/j.molliq.2020.114391.

E.E. Badr, (2017). Preparation, surface-active properties and antimicrobial activities of cationic surfactants based on morpholine and piperidine, Adv. Appl. Sci. Res. 8 (2017) 81–89.

E.M.P. Gómez, O.F. Silva, M. Der Ohannesian, M.N. Fernández, R.G. Oliveira, M.A. Fernández, (2022). Micelle-to-vesicle transition of lipoamino Gemini surfactant induced by metallic salts and its effects on antibacterial activity, J. Mol. Liq. 353 (2022) 118793.

H. Lal, M. Akram, (2022). Physico-chemical characterization of bovine serum albumin-cationic gemini surfactant interaction, J. Mol. Liq. 361 (2022) 119626.

H. Zhu, X. Li, X. Lu, J. Wang, Z. Hu, X. Ma, (2021). Efficiency of Gemini surfactant containing semi-rigid spacer as microbial corrosion inhibitor for carbon steel in simulated seawater, Bioelectrochemistry. 140 (2021) 107809.

I. Sarikaya, S. Bilgen, Y. Ünver, K. Inan Bektas, H. Akbas, (2021). Synthesis, characterization, antibacterial activity, and interfacial and micellar features of novel cationic gemini surfactants with different spacers, J. Surfactants Deterg. 24 (2021) 909–921. https://doi.org/10.1002/jsde.12532.

J. Feng, Z. Yan, J. Song, J. He, G. Zhao, H. Fan, (2021). Study on the structure-activity relationship between the molecular structure of sulfate gemini surfactant and surface activity, thermodynamic properties and foam properties, Chem. Eng. Sci. 245 (2021) 116857.

J. Hao, T. Qin, Y. Zhang, Y. Li, Y. Zhang, (2019). Synthesis, surface properties and antimicrobial performance of novel gemini pyridinium surfactants, Colloids Surfaces B Biointerfaces. 181 (2019) 814–821. https://doi.org/10.1016/j.colsurfb.2019.06.028.

L. Lin, H. Chu, K. Chen, S. Chen, (2019). Surface Properties of Glucose-Based Surfactants and Their Application in Textile Dyeing with Natural Dyes, J. Surfactants Deterg. 22 (2019) 73–83.

L. Lin, X. Li, J. Zhou, J. Zou, J. Lai, Z. Chen, J. Shen, H. Xu, (2021). Plasma-aided green and controllable synthesis of silver nanoparticles and their compounding with gemini surfactant, J. Taiwan Inst. Chem. Eng. 122 (2021) 311–319. https://doi.org/10.1016/j.jtice.2021.04.061.

M. Akram, M. Osama, H. Lal, M. Salim, M.A. Hashmi, K. Din, (2023). Biophysical investigation of the interaction between NSAID ibuprofen and cationic biodegradable Cm-E2O2-Cm gemini surfactants, J. Mol. Liq. 370 (2023) 120972.

M. Mobin, R. Aslam, J. Aslam, (2019). Synergistic effect of cationic gemini surfactants and butanol on the corrosion inhibition performance of mild steel in acid solution, Mater. Chem. Phys. 223 (2019) 623–633.

MSS Khan, AMSA Majid, MA Iqbal, ASA Majid. (2016). Designing the angiogenic inhibitor for brain tumor via disruption of VEGF and IL17A expression, European Journal of Pharmaceutical Sciences, 2016

R. Aslam, M. Mobin, J. Aslam, H. Lgaz, I.-M. Chung, (2019). Inhibitory effect of sodium carboxymethylcellulose and synergistic biodegradable gemini surfactants as effective inhibitors for MS corrosion in 1 M HCl, J. Mater. Res. Technol. 8 (2019) 4521–4533.

R.A. Júnior, J. de Faria Poloni, É.S.M. Pinto, M. Dorn, (2023). Interdisciplinary Overview of Lipopeptide and Protein-Containing Biosurfactants, Genes (Basel). 14 (2023).

S. Tang, X. Meng, F. Wang, Q. Lin, T. Feng, D. Hu, Y. Zhang, (2022). Four Propiconazole Stereoisomers: Stereoselective Bioactivity, Separation via Liquid Chromatography–Tandem Mass Spectrometry, and Dissipation in Banana Leaves, J. Agric. Food Chem. 70 (2022) 877–886.

S.H. Kadhim, (2012). Transition metal complexes with tridentate ligand 1E, 2E-ethanedial (2, 4-dinitro phenyl) hydrazone [5-(2-hydroxy phenyl)-1, 3, 4-oxadiazol-2-yl] hydrazone, J. Thi-Qar Sci. 3 (2012).

V. Kumar, N. Pal, A.K. Jangir, D.L. Manyala, D. Varade, A. Mandal, K. Kuperkar, (2020). Dynamic interfacial properties and tuning aqueous foamability stabilized by cationic surfactants in terms of their structural hydrophobicity, free drainage and bubble extent, Colloids Surfaces A Physicochem. Eng. Asp. 588 (2020) 124362. https://doi.org/10.1016/j.colsurfa.2019.124362.

Y. Liang, H. Li, M. Li, X. Mao, Y. Li, Z. Wang, L. Xue, X. Chen, X. Hao, (2019). Synthesis and physicochemical properties of ester-bonded gemini pyrrolidinium surfactants and a comparison with single-tailed amphiphiles, J. Mol. Liq. 280 (2019) 319–326. https://doi.org/10.1016/j.molliq.2019.02.018.

Z. Lu, G. Zongjie, Z. Qianyu, L. Xueyan, W. Kexin, C. Baoyan, T. Ran, R. Fang, H. Hui, C. Huali, (2023). Preparation and characterization of a gemini surfactant-based biomimetic complex for gene delivery, Eur. J. Pharm. Biopharm. 182 (2023) 92–102. https://doi.org/10.1016/j.ejpb.2022.12.002.