Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts
Abstract
:1. Introduction
2. Results
2.1. Chemistry
2.2. Antifungal Activity
2.3. Antibacterial Activity
2.4. Anticancer Activity
2.5. Morphology Analysis
2.6. Relative Electric Conductivity
2.7. ATP Activity
3. Discussion
4. Materials and Methods
4.1. Materials and Structural Characterization Techniques
4.2. General Procedure for the Synthesis of β-PQA Salts
4.3. Antifungal Activity
4.4. Assay of Minimal Inhibitory Concentration
4.5. Anticancer Activity
4.6. Determination of Cell Membrane Permeability
4.7. Scanning Electron Microscope (SEM) Observations
4.8. Detection of Intracellular ATP
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Ruiz-Gil, T.; Acuña, J.J.; Fujiyoshi, S.; Tanaka, D.; Noda, J.; Maruyama, F.; Jorquera, M.A. Airborne bacterial communities of outdoor environments and their associated influencing factors. Environ. Int. 2020, 145, 106156. [Google Scholar] [CrossRef]
- Dukare, A.S.; Paul, S.; Nambi, V.E.; Gupta, R.K.; Singh, R.; Sharma, K.; Vishwakarma, R.K. Exploitation of microbial antagonists for the control of postharvest diseases of fruits: A review. Crit. Rev. Food Sci. Nutr. 2019, 59, 1498–1513. [Google Scholar] [CrossRef] [PubMed]
- Zhang, M.; Dai, Z.C.; Qian, S.S.; Liu, J.Y.; Xiao, Y.; Lu, A.M.; Zhu, H.L.; Wang, J.X.; Ye, Y.H. Design, synthesis, antifungal, and antioxidant activities of (E)-6-((2-phenylhydrazono)methyl)quinoxaline derivatives. J. Agric. Food Chem. 2014, 62, 9637–9643. [Google Scholar] [CrossRef] [PubMed]
- Scarpino, V.; Reyneri, A.; Sulyok, M.; Krska, R.; Blandino, M. Effect of fungicide application to control Fusarium head blight and 20 Fusarium and Alternaria mycotoxins in winter wheat (Triticum aestivum L.). World Mycotoxin J. 2015, 8, 499–510. [Google Scholar] [CrossRef]
- Carlie, S.M.; Boucher, C.E.; Bragg, R.R. Molecular basis of bacterial disinfectant resistance. Drug Resist. Updat. 2020, 48, 100672. [Google Scholar] [CrossRef] [PubMed]
- Dan, W.; Gao, J.; Li, L.; Xu, Y.; Wang, J.; Dai, J. Cellular and non-target metabolomics approaches to understand the antifungal activity of methylaervine against Fusarium solani. Bioorg. Med. Chem. Lett. 2021, 43, 128068. [Google Scholar] [CrossRef]
- Guo, Y.Y.; Chen, J.B.; Ren, D.; Du, B.D.; Wu, L.; Zhang, Y.Y.; Wang, Z.Y.; Qian, S. Synthesis of osthol-based botanical fungicides and their antifungal application in crop protection. Bioorg. Med. Chem. 2021, 40, 116184. [Google Scholar] [CrossRef]
- Karpiński, T.M. Essential Oils of Lamiaceae Family Plants as Antifungals. Biomolecules 2020, 10, 103. [Google Scholar] [CrossRef] [Green Version]
- Abelan, U.S.; de Oliveira, A.C.; Cacoci, É.S.P.; Martins, T.E.A.; Giacon, V.M.; Velasco, M.V.R.; de Castro Lima, C.R.R. Potential use of essential oils in cosmetic and dermatological hair products: A review. J. Cosmet. Dermatol. 2021. [Google Scholar] [CrossRef]
- Cheng, S.S.; Liu, J.Y.; Hsui, Y.R.; Chang, S.T. Chemical polymorphism and antifungal activity of essential oils from leaves of different provenances of indigenous cinnamon (Cinnamomum osmophloeum). Bioresour. Technol. 2006, 97, 306–312. [Google Scholar] [CrossRef]
- Debbabi, H.; El Mokni, R.; Chaieb, I.; Nardoni, S.; Maggi, F.; Caprioli, G.; Hammami, S. Chemical Composition, Antifungal and Insecticidal Activities of the Essential Oils from Tunisian Clinopodium nepeta subsp. nepeta and Clinopodium nepeta subsp. glandulosum. Molecules 2020, 25, 2137. [Google Scholar] [CrossRef] [PubMed]
- Neuenschwander, U.; Meier, E.; Hermans, I. Peculiarities of β-Pinene Autoxidation. ChemSusChem 2011, 4, 1613–1621. [Google Scholar] [CrossRef]
- Salehi, B.; Upadhyay, S.; Orhan, I.E.; Jugran, A.K.; Jayaweera, S.L.D.; Dias, D.A.; Sharopov, F.; Taheri, Y.; Martins, N.; Baghalpour, N.; et al. Therapeutic Potential of α- and β-Pinene: A Miracle Gift of Nature. Biomolecules 2019, 9, 738. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jiao, Y.; Niu, L.; Ma, S.; Li, J.; Tay, F.R.; Chen, J. Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance. Prog. Polym. Sci. 2017, 71, 53–90. [Google Scholar] [CrossRef] [PubMed]
- Bureš, F. Quaternary Ammonium Compounds: Simple in Structure, Complex in Application. Top. Curr. Chem. 2019, 377, 14. [Google Scholar] [CrossRef] [PubMed]
- Sapozhnikov, S.V.; Sabirova, A.E.; Shtyrlin, N.V.; Druk, A.Y.; Agafonova, M.N.; Chirkova, M.N.; Kazakova, R.R.; Grishaev, D.Y.; Nikishova, T.V.; Krylova, E.S.; et al. Design, synthesis, antibacterial activity and toxicity of novel quaternary ammonium compounds based on pyridoxine and fatty acids. Eur. J. Med. Chem. 2021, 211, 113100. [Google Scholar] [CrossRef] [PubMed]
- Domagk, G. Ein beitrag zur chemotherapie der bakteriellen infektionen. Dtsch. Med. Wochenschr. 1935, 61, 250–253. [Google Scholar] [CrossRef]
- Tischer, M.; Pradel, G.; Ohlsen, K.; Holzgrabe, U. Quaternary ammonium salts and their antimicrobial potential: Targets or nonspecific interactions? ChemMedChem 2012, 7, 22–31. [Google Scholar] [CrossRef] [PubMed]
- Fromm-Dornieden, C.; Rembe, J.D.; Schäfer, N.; Böhm, J.; Stuermer, E.K. Cetylpyridinium chloride and miramistin as antiseptic substances in chronic wound management–prospects and limitations. J. Med. Microbiol. 2015, 64, 407–414. [Google Scholar] [CrossRef] [Green Version]
- Ahmad, A.; Elisha, I.L.; van Vuuren, S.; Viljoen, A. Volatile phenolics: A comprehensive review of the anti-infective properties of an important class of essential oil constituents. Phytochemistry 2021, 190, 112864. [Google Scholar] [CrossRef]
- Li, J.; Tian, X.R.; Gao, Y.Q.; Shang, S.B.; Feng, J.T.; Zhang, X. A value-added use of volatile turpentine: Antifungal activity and QSAR study of β-pinene derivatives against three agricultural fungi. RSC Adv. 2015, 5, 66947–66955. [Google Scholar] [CrossRef]
- Shi, Y.; Si, H.; Wang, P.; Chen, S.; Shang, S.; Song, Z.; Wang, Z.; Liao, S. Derivatization of Natural Compound β-Pinene Enhances Its In Vitro Antifungal Activity against Plant Pathogens. Molecules 2019, 24, 3144. [Google Scholar] [CrossRef] [Green Version]
- Feng, X.Z.; Xiao, Z.Q.; Yang, Y.L.; Chen, S.X.; Liao, S.L.; Luo, H.; He, L.; Wang, Z.D.; Fan, G.R. β-Pinene Derived Products With Enhanced In Vitro Antimicrobial Activity. Nat. Prod. Commun. 2018, 16, 1–8. [Google Scholar]
- Wang, Y.; Wu, C.; Zhang, Q.; Shan, Y.; Gu, W.; Wang, S. Design, synthesis and biological evaluation of novel β-pinene-based thiazole derivatives as potential anticancer agents via mitochondrial-mediated apoptosis pathway. Bioorg. Chem. 2019, 84, 468–477. [Google Scholar] [CrossRef]
- Zhong, W.; Dong, C.; Liuyang, R.; Guo, Q.; Zeng, H.; Lin, Y.; Zhang, A. Controllable synthesis and antimicrobial activities of acrylate polymers containing quaternary ammonium salts. React. Funct. Polym. 2017, 121, 110–118. [Google Scholar] [CrossRef]
- Qin, X.; Li, Y.; Zhou, F.; Ren, L.; Zhao, Y.; Yuan, X. Polydimethylsiloxane-polymethacrylate block copolymers tethering quaternary ammonium salt groups for antimicrobial coating. Appl. Surf. Sci. 2015, 328, 183–192. [Google Scholar] [CrossRef]
- Chen, C.Z.; Beck-Tan, N.C.; Dhurjati, P.; van Dyk, T.K.; LaRossa, R.A.; Cooper, S.L. Quaternary Ammonium Functionalized Poly(propylene imine) Dendrimers as Effective Antimicrobials: Structure−Activity Studies. Biomacromolecules 2000, 1, 473–480. [Google Scholar] [CrossRef] [PubMed]
- Mittal, R.P.; Rana, A.; Jaitak, V. Essential oils: An impending substitute of synthetic antimicrobial agents to overcome antimicrobial resistance. Curr. Drug Targets 2019, 20, 605–624. [Google Scholar] [CrossRef] [PubMed]
- Xu, M.; Xue, H.; Li, X.; Zhao, Y.; Lin, L.; Yang, L.; Zheng, G. Chemical composition, antibacterial properties, and mechanism of Smilax china L. polyphenols. Appl. Microbiol. Biotechnol. 2019, 103, 9013–9022. [Google Scholar] [CrossRef] [PubMed]
- Tao, P.; Wu, C.Y.; Hao, J.; Gao, Y.Q.; He, X.H.; Li, J.; Shang, S.B.; Song, Z.Q.; Song, J. Antifungal Application of Rosin Derivatives from Renewable Pine Resin in Crop Protection. J. Agric. Food Chem. 2020, 68, 4144–4154. [Google Scholar] [CrossRef]
- Cui, H.; Yang, H.; Abdel-Samie, M.A.; Siva, S.; Lin, L. Controlled-release casein/cinnamon essential oil nanospheres for the inactivation of Campylobacter jejuni in duck. Int. J. Food Microbiol. 2021, 341, 109074. [Google Scholar] [CrossRef]
- Han, Y.J.; Sun, Z.C.; Chen, W.X. Antimicrobial Susceptibility and Antibacterial Mechanism of Limonene against Listeria monocytogenes. Molecules 2020, 25, 33. [Google Scholar] [CrossRef] [Green Version]
- Cinthia, S.V.; Sabine, R.; Karsten, M. ATP and Its Metabolite Adenosine as Regulators of Dendritic Cell Activity. Front. Immunol. 2018, 9, 2581. [Google Scholar]
- Chida, J.; Yamane, K.; Takei, T.; Kido, H. An efficient extraction method for quantitation of adenosine triphosphate in mammalian tissues and cells. Anal. Chim. Acta 2012, 727, 8–12. [Google Scholar] [CrossRef]
- Antoci, V.; Oniciuc, L.; Amariucai-Mantu, D.; Moldoveanu, C.; Mangalagiu, V.; Amarandei, A.M.; Lungu, C.N.; Dunca, S.; Mangalagiu, I.I.; Zbancioc, G. Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents. Pharmaceuticals 2021, 14, 335. [Google Scholar] [CrossRef]
- Chen, J.Z.; Xiao, Z.Q.; Xu, L.F.; Wang, Z.D.; Han, Z.J. The synthesis and structural analysis of hydronopyl tertiary amine compounds. J. Jiangxi Normal Univ. 2016, 40, 179–182. [Google Scholar]
- Zhao, L.H.; Xiao, Z.Q.; Chen, J.Z.; Wang, Z.D.; Fan, G.R.; Chen, S.Q. Synthesis and structural analysis of hydronopol and its halides. Chem. Ind. For. Prod. 2012, 32, 39–42. [Google Scholar]
- Zhu, J.K.; Gao, J.M.; Yang, C.J.; Shang, X.F.; Zhao, Z.M.; Lawoe, R.K.; Zhou, R.; Sun, Y.; Yin, X.D.; Liu, Y.Q. Design, synthesis, and antifungal evaluation of neocryptolepine derivatives against phytopathogenic fungi. J. Agric. Food Chem. 2020, 68, 2306–2315. [Google Scholar] [CrossRef] [PubMed]
- Mishra, V.R.; Ghanavatkar, C.W.; Mali, S.N.; Qureshi, S.I.; Chaudhari, H.K.; Sekar, N. Design, synthesis, antimicrobial activity and computational studies of novel azo linked substituted benzimidazole, benzoxazole and benzothiazole derivatives. Comput. Biol. Chem. 2019, 78, 330–337. [Google Scholar] [CrossRef] [PubMed]
- Silva, A.; Nobre, H.; Sampaio, L.; Nascimento, B.; Silva, C.; Neto, J.B.A.; Manresa, Á.; Pinazo, A.; Cavalcanti, B.; Moraes, M.O.; et al. Antifungal and antiprotozoal green amino acid-based rhamnolipids: Mode of action, antibiofilm efficiency and selective activity against resistant Candida spp. strains and Acanthamoeba castellanii. Colloids Surf. B 2020, 193, 111148. [Google Scholar] [CrossRef]
- Gong, R.; Li, Z.Q.; Fu, K.; Ma, C.; Wang, W.; Chen, J.C. Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma. Exp. Neurobiol. 2021, 30, 244–255. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Wang, C.; Dong, H.; Wang, X.; Gao, F.; Zhang, S.; Zhang, X. Aspirin has a better effect on PIK3CA mutant colorectal cancer cells by PI3K/Akt/Raptor pathway. Mol. Med. 2020, 26, 14. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yin, X.D.; Ma, K.Y.; Wang, Y.L.; Sun, Y.; Shang, X.F.; Zhao, Z.M.; Wang, R.X.; Chen, Y.J.; Zhu, J.K.; Liu, Y.Q. Design, synthesis, and antifungal evaluation of 8-hydroxyquinoline metal complexes against phytopathogenic fungi. J. Agric. Food Chem. 2020, 68, 11096–11104. [Google Scholar] [CrossRef]
- Yin, X.D.; Sun, Y.; Lawoe, R.K.; Yang, G.Z.; Liu, Y.Q.; Shang, X.F.; Liu, H.; Yang, Y.D.; Zhu, J.-K.; Huang, X.L. Synthesis and anti-phytopathogenic activity of 8-hydroxyquinoline derivatives. RSC Adv. 2019, 9, 30087–30099. [Google Scholar] [CrossRef] [Green Version]
Fungi | The Value of EC50 (μg/mL) | ||||||
---|---|---|---|---|---|---|---|
4a | 4b | 4c | 4d | 4e | 4f | Ch. | |
F. oxysporum f.sp. niveum | 4.5 | 17.42 | 40.82 | 49.63 | 50.53 | 391.04 | 3.98 |
P. nicotianae var.nicotianae | 10.92 | 15.1 | 10.54 | 229.37 | 94.06 | 189.69 | 1.81 |
C. acutatum | 27.09 | 18.21 | 19.58 | 52.94 | 33.31 | 168.86 | 27.09 |
R. solani | 9.45 | 10.97 | 9.36 | 24.62 | 11.77 | 74.83 | 0.43 |
C. versicolor | 31.98 | 27.83 | 77.68 | 113.18 | 296.61 | 26411.41 | 2.41 |
F. verticillioides | 15.09 | 10.78 | 20.67 | 46.15 | 36.81 | 61.94 | 0.67 |
D. pinea | 10.82 | 18.85 | 14.32 | 906.84 | 81.94 | 203.9 | 1.74 |
P. vaporaria | 18.01 | 13.71 | 11.02 | 181.88 | 165.09 | 306.31 | 0.07 |
Fusicoccumaesculi | 6.34 | 5.39 | 10.25 | 32.56 | 40.37 | 93.84 | 0.09 |
C. gloeosprioides | 33.76 | 18.98 | 21.13 | 32.12 | 36.03 | 398.38 | 2.05 |
Bacteria | The Value of MIC (μg/mL) | ||||||
---|---|---|---|---|---|---|---|
4a | 4b | 4c | 4d | 4e | 4f | Chloramphenicol | |
E. coli | 2.5 | 20 | 80 | 160 | 160 | 320 | 5 |
P. aeruginosa | 0.625 | 80 | 160 | 160 | 80 | 320 | 80 |
S. aureus | 1.25 | 80 | 80 | 320 | 80 | 320 | 0.625 |
B. subtilis | 1.25 | 5 | 80 | 160 | 160 | 640 | 0.625 |
Compound | IC50 (μM) | |
---|---|---|
HCT-116 | MCF-7 | |
4a | 11.22 | 11.63 |
4b | 8.16 | 2.46 |
4c | 1.10 | 2.43 |
4d | 201.90 | 180.30 |
4e | 107.80 | 57.08 |
4f | 25.54 | 15.16 |
Sorafenib | 20.79 | 13.92 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Zhang, L.; Feng, X.-Z.; Xiao, Z.-Q.; Fan, G.-R.; Chen, S.-X.; Liao, S.-L.; Luo, H.; Wang, Z.-D. Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts. Int. J. Mol. Sci. 2021, 22, 11299. https://doi.org/10.3390/ijms222011299
Zhang L, Feng X-Z, Xiao Z-Q, Fan G-R, Chen S-X, Liao S-L, Luo H, Wang Z-D. Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts. International Journal of Molecular Sciences. 2021; 22(20):11299. https://doi.org/10.3390/ijms222011299
Chicago/Turabian StyleZhang, Li, Xue-Zhen Feng, Zhuan-Quan Xiao, Guo-Rong Fan, Shang-Xing Chen, Sheng-Liang Liao, Hai Luo, and Zong-De Wang. 2021. "Design, Synthesis, Antibacterial, Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts" International Journal of Molecular Sciences 22, no. 20: 11299. https://doi.org/10.3390/ijms222011299