The amoebicidal effect of New Bioactive o-Phenylenediamine Surface Functionalized Poly (Maleic Anhydride-alt-Vinyl Acetate) and Citric Acid Derived Carbon Quantum Nanodot-Based Conjugates on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials

Necati Özpınar; Nihat Karakuş; Tutku Tunç; Ather Farooq Khan; Gülderen Karakuş

doi:10.19127/mbsjohs.1787320

EN

The amoebicidal effect of New Bioactive o-Phenylenediamine Surface Functionalized Poly (Maleic Anhydride-alt-Vinyl Acetate) and Citric Acid Derived Carbon Quantum Nanodot-Based Conjugates on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials

Abstract

Objective: This study aimed to evaluate the amoebicidal activity of o-phenylenediamine (o-PDA)-conjugated carrier systems, including maleic anhydride-vinyl acetate alternating copolymer (MAVA) and citric acid-derived carbon quantum dots (CNDs), against Acanthamoeba castellanii cysts and trophozoites. Additionally, the cytotoxicity of these compounds was assessed on the HT-22 Mouse Hippocampal Neuronal cell line. Method: Two non-toxic carrier systems were synthesized: MAVA via charge transfer complex (CTC) radical polymerization, and CNDs via rapid thermal pyrolysis of citric acid. o-PDA surface conjugation was achieved through an amide mechanism after the ring-opening reaction. The synthesized compounds were tested for their amoebicidal effects on A. castellanii cysts and trophozoites, while cytotoxicity analyses were conducted using the HT-22 neuronal cell line. Results: According to our findings, the cytotoxicity of all compounds at the tested concentrations was within an acceptable range. When examining the amoebicidal activities, it was observed that MAVA at concentrations of 0.01 g/mL and 0.005 g/mL did not have any viable trophozoites, while CNDs at a concentration of 0.01 g/mL did not have any viable cysts. Overall, all compounds showed significant amoebicidal activity. Conclusion: Our findings demonstrate a strong dose-dependent amoebicidal effect of these substances on A. castellanii cysts and trophozoites. It is believed that these substances, supported by in vivo experiments, could potentially serve as new therapeutic agents.

Keywords

Carbon quantum nanodots (CNDs) , maleic anhydride-vinyl acetate alternating copolymer (MAVA) , surface modification , o-phenylenediamine (o-PDA) , A. castellanii

References

Fabres L F, dos Santos SPR, Benitez LB & Rott MB. Isolation and identification of Acanthamoeba spp. from thermal swimming pools and spas in Southern Brazil. Acta Parasitologica 2016; 61, 221-227. https://doi.org/10.1515/ap-2016-0031
Saburi E, Rajaii T, Behdari A, Kohansal MH. & Vazini H. Free-living amoebae in the water resources of Iran: a systematic review. Journal of Parasitic Diseases 2017; 41, 919-928. https://doi.org/10.1007/s12639-017-0950-2
Xuan Y, Shen Y, Ge Y, Yan G & Zheng S. Isolation and identification of Acanthamoeba strains from soil and tap water in Yanji, China. Environmental Health and Preventive Medicine 2017; 22-58. https://doi.org/10.1186/s12199-017-0655-2
Ozcelik S, Yunlu O & Ozpinar N. Isolation and morphotyping of Acanthamoeba spp. and Vermamoeba spp. from hospital air-conditioning systems. Cumhuriyet Medical Journal 2017; 39, 369-373. https://doi.org/ 10.7197/cmj.v39i1.5000194070
Kot K, Lanocha-Arendarczyk NA & Kosik-Bogacka DI. Amoebas from the genus Acanthamoeba and their pathogenic properties. Annals of Parasitology, 2018; 64(4). https://doi.org/ 10.17420/ap6404.164
Ozpinar N, Culha G, Kaya T & Yucel H. The amoebicidal activity of three substances derived from benzothiazole on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials. Acta Tropica 2021; 220, 105981. https://doi.org/10.1016/j.actatropica.2021.105981
Ozpinar N, Ozpinar H, Bakay BB & Tunc T. Amoebicidal activity of benzothiazole on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials. Acta Tropica 2020; 203, 105322. https://doi.org/10.1016/j.actatropica.2019.105322
Shing B, Singh S, Podust LM. The antifungal drug isavuconazole is both amoebicidal and cysticidal against Acanthamoeba castellanii. Antimicrobial agents and chemotherapy 2020; 64:10.1128/aac. 02223-02219
Duncan R. Polymer conjugates for tumour targeting and intracytoplasmic delivery. The EPR effect as a common gateway?. Pharmaceutical Science & Technology Today. 1999; 2, 441-449.
Yao B, Huang H, Liu Y & Kang Z. Carbon dots: a small conundrum. Trends in Chemistry 2019; 1, 235-246. https://doi.org/10.1016/j.trechm.2019.02.003

Roy P, Chen PC, Periasamy AP, Chen YN & Chang HT. Photoluminescent carbon nanodots: synthesis, physicochemical properties and analytical applications. Materials Today 2015; 18, 447-458. https://doi.org/10.1016/j.mattod.2015.04.005
Thangaraj B, Solomon PR & Ranganathan S. Synthesis of carbon quantum dots with special reference to biomass as a source-a review. Current Pharmaceutical Design 2019; 25, 1455-1476. https://doi.org/10.2174/1381612825666190618154518
Rigodanza F, Burian M, Arcudi F, Đorđević L, Amenitsch H & Prato M. Snapshots into carbon dots formation through a combined spectroscopic approach Nature Communications 2021; 12, 2640. https://doi.org/10.1038/s41467-021-22902-w
Aydemir O, Terzi HA, Köroğlu M, Altındiş M. Piperacillin / tazobactam in-vitro activity in Escherichia coli and Klebsiella pneumoniae strains with extended spectrum beta-lactamase production. Online Turkish Journal of Health Sciences. 2019;4(2):118-27.
Zheng D, Li B, Li C, Fan J, Lei Q, Li C, Xu Z & Zhang X. Carbondot-decorated carbon nitride nanoparticles for enhanced photodynamic therapy against hypoxic tumor via water splitting. ACS Nano. 2016; 10 (9), 8715–8722. https://doi.org/10.1021/acsnano.6b04156
Ren J, Malfatti L & Innocenzi P. Citric acid derived carbon dots, the challenge of understanding the synthesis-structure relationship. C, 2021; 7(1), 2. https://doi.org/10.3390/c7010002
Mansuriya BD & Altintas Z. Carbon dots: classification, properties, synthesis, characterization, and applications in health care an updated review (2018–2021). Nanomaterials. 2021; 11, 2525. https://doi.org/10.3390/nano11102525
Meloni M, Stagi L, Sanna D, Garroni S, Calvillo L, Terracina A, Cannas M, Messina F, Carbonaro CM & Innocenzi P. Harnessing molecular fluorophores in the carbon dots matrix: the case of safranin O. Nanomaterials 2022; 12, 2351. https://doi.org/10.3390/nano12142351
Zhang Z, Fraser A, Ye S, Merle G & Barralet J. Top-down bottom-up graphene synthesis. Nano Futures 2019; 3, 042003. https://doi.org/ 10.1088/2399-1984/ab4eff
Olatomiwa AL, Adam T, Gopinath SC, Kolawole SY, Olayinka OH & Hashim U. Graphene synthesis, fabrication, characterization based on bottom-up and top-down approaches: An overview. Journal of Semiconductors 2022; 43, 061101. https://doi.org/ 10.1088/1674-4926/43/6/061101
Yan F, Jiang Y, Sun X, Bai Z, Zhang Y & Zhou X. Surface modification and chemical functionalization of carbon dots: a review. Microchimica Acta 2018; 185, 1-34. https://doi.org/10.1007/s00604-018-2953-9
Shehab WS, Aziz MA, Elhoseni NKR, Assy MG, Abdellattif MH & Hamed EO. Design, synthesis, molecular docking, and evaluation antioxidant and antimicrobial activities for novel 3-phenylimidazolidin-4-one and 2-aminothiazol-4-one derivatives. Molecules 2022; 27, 767. https://doi.org/10.3390/molecules27030767
Karakus G. Design, Synthesis and Characterization of 1, 2-Phenylenediamine Functionalized Poly (Maleic Anhydride-alt-Vinyl Acetate) as a Potential New Bioactive Formulation. Hittite Journal of Science and Engineering 2022; 9, 305-311. https://doi.org/10.17350/HJSE19030000284
Karakus G, Polat ZA, Yenidunya AF, Zengin HB & Karakus CB. Synthesis, characterization and cytotoxicity of novel modified poly [(maleic anhydride)‐co‐(vinyl acetate)]/noradrenaline conjugate. Polymer international 2013; 62, 492-500. https://doi.org/10.1002/pi.4341
Karakuş G. Synthesis, structural characterization, and water solubility of a novel modified poly maleic anhydride-co-vinyl acetate/acriflavine conjugate. Hacettepe Journal of Biology and Chemistry. 2016; 44, 549-558.
Karakus G, Can HK & Yaglioglu AS. Synthesis, structural characterization, thermal behavior and cytotoxic/antiproliferative activity assessments of poly (maleic anhydride-alt-acrylic acid)/hydroxyurea polymer/drug conjugate. Journal of Molecular Structure 2020; 1210, 127989. https://doi.org/10.1016/j.molstruc.2020.127989
Karakus G, Yaglioglu AS, Zengin H & Karakus N. Synthesis, characterization and antiproliferative activities of novel modified poly (maleic anhydride-co-vinyl acetate)/cytosine β-Darabinofuranoside hydrochloride conjugate. Marmara Pharmaceutical Journal 2015; 19, 73-81. https://doi.org/ 10.12991/mpj.2015198613
Jensen T, Barnes WG & Meyers D. Axenic cultivation of large populations of Acanthamoeba castellanii (JBM). The Journal of Parasitology, 1970; 904-906. https://doi.org/10.2307/3277503
Moon EK, Chung DI, Hong YC, Ahn TI & Kong HH. Acanthamoeba castellanii: gene profile of encystation by ESTs analysis and KOG assignment. Experimental Parasitology 2008; 119, 111-116. https://doi.org/10.1016/j.exppara.2008.01.001
Lorenzo-Morales J, Martín-Navarro CM, López-Arencibia A, Santana-Morales MA, Afonso-Lehmann RN, Maciver SK, Valladares B & Martínez-Carretero E. Therapeutic potential of a combination of two gene-specific small interfering RNAs against clinical strains of Acanthamoeba. Antimicrobial Agents and Chemotherapy 2010; 54, 5151-5155. https://doi.org/10.1128/aac.00329-10
Mengue L, Régnacq M, Aucher W, Portier E, Héchard Y & Samba-Louaka A. Legionella pneumophila prevents proliferation of its natural host Acanthamoeba castellanii. Scientific Reports 2016; 6, 36448. https://doi.org/ 10.1038/srep36448
Kazacos KR, Jelicks LA & Tanowitz HB. Baylisascaris larva migrans. Handbook of Clinical Neurology, 2013; 114, 251-262. https://doi.org/10.1016/B978-0-444-53490-3.00020-0
Marciano-Cabral F & Cabral G. Acanthamoeba spp. as agents of disease in humans. Clinical Microbiology Reviews. 2003; 16(2), 273-307. https://doi.org/10.1128/cmr.16.2.273-307.2003
Clarke M, Lohan AJ, Liu B, Lagkouvardos I, Roy S, Zafar N, Bertelli C, Schilde C, Kianianmomeni A, Bürglin TR. et al. Genome of Acanthamoeba castellanii highlights extensive lateral gene transfer and early evolution of tyrosine kinase signaling. Genome Biology 2013; 14, 1-15.
Oldenburg CE, Acharya NR, Tu EY, Zegans ME, Mannis MJ, Gaynor BD, Whitcher JP, Lietman TM & Keenan JD. Practice patterns and opinions in the treatment of acanthamoeba keratitis. Cornea 2011; 30, 1363. https://doi.org/ 10.1097/ICO.0b013e31820f7763
Anwar A, Khan NA & Siddiqui R. Combating Acanthamoeba spp. cysts: what are the options?. Parasites & Vectors 2018; 11, 1-6. https://doi.org/ 10.1186/s13071-017-2572-z
Turner N, Russell A, Furr J & Lloyd D. Emergence of resistance to biocides during differentiation of Acanthamoeba castellanii. Journal of Antimicrobial Chemotherapy 2000; 46, 27-34. https://doi.org/10.1093/jac/46.1.27
Karakuş G, Malatyalı E, Zengin H & Değerli S. In vitro amoebicidal activity of poly (maleic anhydride-co-vinyl acetate) copolymer on Acanthamoeba spp. trophozoites and cysts. Basic and Clinical Sciences, 2013;2, 1-14. https://doi.org/10.12808/bcs.v2i1.16

Details

Primary Language

English

Subjects

Clinical Microbiology

Journal Section

Research Article

Authors

Necati Özpınar ^*
0000-0002-7317-885X
Türkiye

Nihat Karakuş
0000-0001-6223-7669
Türkiye

Tutku Tunç
0000-0002-8274-9386
Türkiye

Ather Farooq Khan
0000-0002-5178-2482
Pakistan

Gülderen Karakuş
0000-0003-2596-9208
Türkiye

Publication Date

November 30, 2025

Submission Date

September 25, 2025

Acceptance Date

October 16, 2025

Published in Issue

Year 2025 Volume: 11 Number: 4

DOI

https://doi.org/10.19127/mbsjohs.1787320

IZ

https://izlik.org/JA39WT53NM

Vancouver

1.Necati Özpınar, Nihat Karakuş, Tutku Tunç, Ather Farooq Khan, Gülderen Karakuş. The amoebicidal effect of New Bioactive o-Phenylenediamine Surface Functionalized Poly (Maleic Anhydride-alt-Vinyl Acetate) and Citric Acid Derived Carbon Quantum Nanodot-Based Conjugates on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials. Mid Blac Sea J Health Sci. 2025 Nov. 1;11(4):383-400. doi:10.19127/mbsjohs.1787320

Öz

The amoebicidal effect of New Bioactive o-Phenylenediamine Surface Functionalized Poly (Maleic Anhydride-alt-Vinyl Acetate) and Citric Acid Derived Carbon Quantum Nanodot-Based Conjugates on Acanthamoeba castellanii cysts and trophozoites and its cytotoxic potentials

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