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Environmental Fate, Ecotoxicity, and Remediation of Heterocyclic Pharmaceuticals as Emerging Contaminants: A Review of Long-Term Risks and Impacts

Oussama Baaloudj, Laura Scrano, Sabino Aurelio Bufo, Lee-Ann Sade Modley, Filomena Lelario, Angelica Rebecca Zizzamia, Lucia Emanuele, Monica Brienza

Organics · pp. 1–1 · Published 2 Jan 2025

10.3390/org6010001

Abstract

Heterocyclic pharmaceuticals are emerging contaminants due to their toxic, carcinogenic nature and detrimental impact on the natural ecosystem. These compounds pose a significant environmental concern given their widespread use in medical therapy, constituting over 90% of new medications. Their unique chemical structure contributes to their persistence in various environmental matrices, necessitating urgent measures to mitigate their risks. This review comprehensively examines the sources, environmental fate, toxicity, and long-term risks associated with heterocyclic pharmaceuticals, proposing potential remediation strategies. The article commences with an overview of the diverse types of heterocyclic pharmaceuticals and their applications, focusing on compounds containing heteroatoms such as nitrogen, oxygen, and sulfur. Subsequently, it explores the sources and pathways through which these pollutants enter the environment, including wastewater discharge, agricultural runoff, improper disposal, resistance to biodegradation, and bioaccumulation. The toxic effects and long-term consequences of exposure to heterocyclic pharmaceuticals are then discussed, encompassing neurotoxicity, genotoxicity, mutagenesis, cardiovascular and metabolic toxicity, carcinogenicity, and teratogenesis. Additionally, this review summarizes various remediation strategies and treatment solutions aimed at reducing the environmental impact of these compounds, drawing insights from the literature. The research concludes by identifying critical areas for future research, emphasizing the urgent need for more effective remediation strategies to address the growing concern posed by these emerging contaminants.

Ecotoxicity Environmental remediation Environmental science Environmental chemistry Term (time) Contamination Environmental protection Chemistry

References (112)

  1. 1 Taylor, 2016, Modern advances in heterocyclic chemistry in drug discovery [DOI]
  2. 2 Kabir, 2022, A review on biological and medicinal impact of heterocyclic compounds [DOI]
  3. 3 Aryal, 2020, Transformation products of pharmaceuticals in the environment: Their fate, (eco)toxicity and bioaccumulation potential
  4. 4 Broughton, 2004, Selection of heterocycles for drug design [DOI]
  5. 5 Lamberth, C., and Dinges, J. (2012). Bioactive Heterocyclic Compound Classes: Agrochemicals, Wiley. [DOI]
  6. 6 Lu, 2012, Development of cascade reactions for the concise construction of diverse heterocyclic architectures [DOI]
  7. 7 Dua, 2011, Pharmacological significance of synthetic heterocycles scaffold: A review
  8. 8 Carmona, 2022, Pharmaceuticals as emerging pollutants: Case naproxen an overview [DOI]
  9. 9 Tao, 2022, Environmental fate and toxicity of androgens: A critical review [DOI]
  10. 10 Jampilek, J. (2019). Heterocycles in Medicinal Chemistry. Molecules, 24. [DOI]
  11. 11 Li Petri, G., Holl, R., Spanò, V., Barreca, M., Sardo, I., and Raimondi, M.V. (2023). Editorial: Emerging heterocycles as bioactive compounds. Front. Chem., 11. [DOI]
  12. 12 Sadek, 2023, Recent developments in the synthesis of hybrid heterocycles, a promising approach to develop multi-target antibacterial agents [DOI]
  13. 13 Lamberth, 2013, Heterocyclic chemistry in crop protection [DOI]
  14. 14 Va, 2017, Application of Synthetic Low Molecular Weight Heterocyclic Compounds Derivatives of Pyrimidine, Pyrazole and Oxazole in Agricultural Biotechnology as a New Plant Growth Regulating Substances [DOI]
  15. 15 Babu, A., Sunil, K., Sajith, A.M., Reddy, E.K., Santra, S., Zyryanov, G.V., Venkatesh, T., Bhadrachari, S., and Nibin Joy, M. (2024). NMI-SO2Cl2-Mediated Amide Bond Formation: Facile Synthesis of Some Dihydrotriazolopyrimidine Amide Derivatives as Potential Anti-Inflammatory and Anti-Tubercular Agents. Pharmaceuticals, 17. [DOI]
  16. 16 Brendel, 2018, Four selected high molecular weight heterocyclic aromatic hydrocarbons: Ecotoxicological hazard assessment, environmental relevance and regulatory needs under REACH [DOI]
  17. 17 González-Andrés, P., Fernández-Peña, L., Díez-Poza, C., Villalobos, C., Nuñez, L., and Barbero, A. (2021). Marine Heterocyclic Compounds That Modulate Intracellular Calcium Signals: Chemistry and Synthesis Approaches. Mar. Drugs, 19. [DOI]
  18. 18 Khetan, 2007, Human Pharmaceuticals in the Aquatic Environment: A Challenge to Green Chemistry [DOI]
  19. 19 Padoley, 2008, Heterocyclic nitrogenous pollutants in the environment and their treatment options—An overview [DOI]
  20. 20 Ghosh, P., and Mukherji, S. (2021). Environmental contamination by heterocyclic Polynuclear aromatic hydrocarbons and their microbial degradation. Bioresour. Technol., 341. [DOI]
  21. 21 Boreen, 2004, Photochemical fate of sulfa drugs in then aquatic environment: Sulfa drugs containing five-membered heterocyclic groups [DOI]
  22. 22 Hou, 2022, Triadimefon in aquatic environments: Occurrence, fate, toxicity, and ecological risk [DOI]
  23. 23 Cordoba, A., Saldias, C., Urzúa, M., Montalti, M., Guernelli, M., Focarete, M.L., and Leiva, A. (2022). On the Versatile Role of Electrospun Polymer Nanofibers as Photocatalytic Hybrid Materials Applied to Contaminated Water Remediation: A Brief Review. Nanomaterials, 12. [DOI]
  24. 24 Gupta, 2011, A review of TiO2 nanoparticles [DOI]
  25. 25 Ahmed, 2017, Progress in the biological and chemical treatment technologies for emerging contaminant removal from wastewater: A critical review [DOI]
  26. 26 Asfaha, 2021, Hybrid process of electrocoagulation and electrooxidation system for wastewater treatment: A review [DOI]
  27. 27 Wang, 2020, Disinfection technology of hospital wastes and wastewater: Suggestions for disinfection strategy during coronavirus Disease 2019 (COVID-19) pandemic in China [DOI]
  28. 28 Bergamasco, 2011, Performance of a coagulation-ultrafiltration hybrid process for water supply treatment [DOI]
  29. 29 Ashrafi, 2015, Wastewater treatment in the pulp-and-paper industry: A review of treatment processes and the associated greenhouse gas emission [DOI]
  30. 30 Qadir, T., Amin, A., Sharma, P.K., Jeelani, I., and Abe, H. (2022). A Review on Medicinally Important Heterocyclic Compounds. Open Med. Chem. J., 16. [DOI]
  31. 31 Sharma, 2020, Recent advancements in the development of heterocyclic anti-inflammatory agents [DOI]
  32. 32 Khandale, 2023, Exploring Potential of Indole Derivatives: A Brief Review [DOI]
  33. 33 Kumari, A., and Singh, R.K. (2019). Medicinal chemistry of indole derivatives: Current to future therapeutic prospectives. Bioorg. Chem., 89. [DOI]
  34. 34 Mushtaq, 2023, Synthesis of biologically active sulfonamide-based indole analogs: A review [DOI]
  35. 35 Hao, 2006, Determination of pharmaceuticals in environmental waters by liquid chromatography/electrospray ionization/tandem mass spectrometry [DOI]
  36. 36 Tahlan, S., Kumar, S., and Narasimhan, B. (2019). Pharmacological significance of heterocyclic 1H-benzimidazole scaffolds: A review. BMC Chem., 13. [DOI]
  37. 37 Gaba, 2016, Development of drugs based on imidazole and benzimidazole bioactive heterocycles: Recent advances and future directions [DOI]
  38. 38 Brishty, S.R., Hossain, M.J., Khandaker, M.U., Faruque, M.R.I., Osman, H., and Rahman, S.M.A. (2021). A Comprehensive Account on Recent Progress in Pharmacological Activities of Benzimidazole Derivatives. Front. Pharmacol., 12. [DOI]
  39. 39 Daghrir, 2013, Tetracycline antibiotics in the environment: A review [DOI]
  40. 40 Hashem, 2021, An overview on novel synthetic approaches and medicinal applications of benzimidazole compounds: An overview on novel synthetic approaches and medicinal applications [DOI]
  41. 41 Keri, 2015, Comprehensive review in current developments of benzimidazole-based medicinal chemistry [DOI]
  42. 42 Costa, R.F., Turones, L.C., Cavalcante, K.V.N., Rosa Júnior, I.A., Xavier, C.H., Rosseto, L.P., Napolitano, H.B., da Silva Castro, P.F., Neto, M.L.F., and Galvão, G.M. (2021). Heterocyclic Compounds: Pharmacology of Pyrazole Analogs from Rational Structural Considerations. Front. Pharmacol., 12. [DOI]
  43. 43 Kumar, 2013, Pyrazole scaffold: A remarkable tool in the development of anticancer agents [DOI]
  44. 44 Adardour, M., Ait Lahcen, M., Oubahmane, M., Ettahiri, W., Hdoufane, I., Bouamama, H., Alanazi, M.M., Cherqaoui, D., Taleb, M., and Garcia, E.Z. (2023). Design, Synthesis, Molecular Modeling and Biological Evaluation of Novel Pyrazole Benzimidazolone Derivatives as Potent Antioxidants. Pharmaceuticals, 16. [DOI]
  45. 45 Gado, 2020, Synthesis and anti-rotavirus activity of some nitrogen heterocycles integrated with pyrazole scaffold [DOI]
  46. 46 Kabi, A.K., Sravani, S., Gujjarappa, R., Garg, A., Vodnala, N., Tyagi, U., Kaldhi, D., Singh, V., Gupta, S., and Malakar, C.C. (2022). Overview on Biological Activities of Pyrazole Derivatives. Materials Horizons: From Nature to Nanomaterials, Springer. [DOI]
  47. 47 Zhang, 2018, Recent advance in oxazole-based medicinal chemistry [DOI]
  48. 48 Atmaram, 2022, Biological activity of oxadiazole and thiadiazole derivatives [DOI]
  49. 49 Joshi, 2023, Review on Chemistry of Oxazole derivatives: Current to Future Therapeutic Prospective
  50. 50 Safarzaei, 2018, Synthesis of 3-aminoisoxazolmethylnaphthols via one-pot three-component reaction under solvent-free conditions [DOI]
  51. 51 Pathania, 2019, Role of sulphur-heterocycles in medicinal chemistry: An update [DOI]
  52. 52 Pathania, S., and Chawla, P.A. (2020). Thiophene-based derivatives as anticancer agents: An overview on decade’s work. Bioorg. Chem., 101. [DOI]
  53. 53 Ingall, 1984, Thiopyrans and Fused Thiopyrans
  54. 54 Laxmikeshav, 2022, Expedition of sulfur-containing heterocyclic derivatives as cytotoxic agents in medicinal chemistry: A decade update [DOI]
  55. 55 Arshad, M.F., Alam, A., Alshammari, A.A., Alhazza, M.B., Alzimam, I.M., Alam, M.A., Mustafa, G., Ansari, M.S., Alotaibi, A.M., and Alotaibi, A.A. (2022). Thiazole: A Versatile Standalone Moiety Contributing to the Development of Various Drugs and Biologically Active Agents. Molecules, 27. [DOI]
  56. 56 Niu, 2023, Application and synthesis of thiazole ring in clinically approved drugs [DOI]
  57. 57 Ayati, 2015, Recent applications of 1,3-thiazole core structure in the identification of new lead compounds and drug discovery [DOI]
  58. 58 Chhabria, 2016, Thiazole: A Review on Chemistry, Synthesis and Therapeutic Importance of its Derivatives [DOI]
  59. 59 Khidre, R.E., and Radini, I.A.M. (2021). Design, synthesis and docking studies of novel thiazole derivatives incorporating pyridine moiety and assessment as antimicrobial agents. Sci. Rep., 11. [DOI]
  60. 60 Dawood, K.M., Raslan, M.A., Abbas, A.A., Mohamed, B.E., Abdellattif, M.H., Nafie, M.S., and Hassan, M.K. (2021). Novel Bis-Thiazole Derivatives: Synthesis and Potential Cytotoxic Activity Through Apoptosis With Molecular Docking Approaches. Front. Chem., 9. [DOI]
  61. 61 Hussain, R., Rehman, W., Khan, S., Maalik, A., Hefnawy, M., Alanazi, A.S., Khan, Y., and Rasheed, L. (2023). Imidazopyridine-Based Thiazole Derivatives as Potential Antidiabetic Agents: Synthesis, In Vitro Bioactivity, and In Silico Molecular Modeling Approach. Pharmaceuticals, 16. [DOI]
  62. 62 Majumdar, 2020, Recent advancements in visible-light-assisted photocatalytic removal of aqueous pharmaceutical pollutants [DOI]
  63. 63 Masanabo, 2023, Advances in polymer-based detection of environmental ibuprofen in wastewater [DOI]
  64. 64 Ghosh, 2023, Fate, detection technologies and toxicity of heterocyclic PAHs in the aquatic and soil environments [DOI]
  65. 65 Caban, 2021, How to decrease pharmaceuticals in the environment? A review [DOI]
  66. 66 Baaloudj, 2021, Simultaneous removal of antibiotics and inactivation of antibiotic-resistant bacteria by photocatalysis: A review [DOI]
  67. 67 Tomas, 2017, Disposal of unused drugs: Knowledge and behavior among people around the world
  68. 68 Karungamye, 2022, The pharmaceutical disposal practices and environmental contamination: A review in East African countries [DOI]
  69. 69 Zhang, 2023, New insight into fate and transport of organic compounds from pollution sources to aquatic environment using non-targeted screening: A wastewater treatment plant case study [DOI]
  70. 70 Kumar, 2019, Recent advances in nano-Fenton catalytic degradation of emerging pharmaceutical contaminants [DOI]
  71. 71 Wang, 2021, Ecotoxicological effects, environmental fate and risks of pharmaceutical and personal care products in the water environment: A review [DOI]
  72. 72 Papaioannou, C., Geladakis, G., Kommata, V., Batargias, C., and Lagoumintzis, G. (2023). Insights in Pharmaceutical Pollution: The Prospective Role of eDNA Metabarcoding. Toxics, 11. [DOI]
  73. 73 Barzegar, 2019, Heterocyclic aromatic amines in cooked food: A review on formation, health risk-toxicology and their analytical techniques [DOI]
  74. 74 Khan, 2022, Heterocyclic amines in cooked meat products, shortcomings during evaluation, factors influencing formation, risk assessment and mitigation strategies [DOI]
  75. 75 Bellamri, 2021, Metabolism and biomarkers of heterocyclic aromatic amines in humans [DOI]
  76. 76 Honda, M., and Suzuki, N. (2020). Toxicities of polycyclic aromatic hydrocarbons for aquatic animals. Int. J. Environ. Res. Public Health, 17. [DOI]
  77. 77 Geng, 2024, Heterocyclic Amines in Meat and Meat Products: Occurrence, Formation, Mitigation, Health Risks and Intervention [DOI]
  78. 78 Cao, W., Yuan, J., Geng, S., Zou, J., Dou, J., and Fan, F. (2023). Oxygenated and Nitrated Polycyclic Aromatic Hydrocarbons: Sources, Quantification, Incidence, Toxicity, and Fate in Soil—A Review Study. Processes, 11. [DOI]
  79. 79 Tangvarasittichai, 2015, Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus [DOI]
  80. 80 Stolte, 2023, NSO-heterocyclic PAHs—Controlled exposure study reveals high acute aquatic toxicity [DOI]
  81. 81 Barbuceanu, S.F., Rosca, E.V., Apostol, T.V., Socea, L.I., Draghici, C., Farcasanu, I.C., Ruta, L.L., Nitulescu, G.M., Iscrulescu, L., and Pahontu, E.M. (2023). New Heterocyclic Compounds from Oxazol-5(4H)-one and 1,2,4-Triazin-6(5H)-one Classes: Synthesis, Characterization and Toxicity Evaluation. Molecules, 28. [DOI]
  82. 82 2024, Addressing the microplastic crisis: A multifaceted approach to removal and regulation [DOI]
  83. 83 Paut Kusturica, M., Jevtic, M., and Ristovski, J.T. (2022). Minimizing the environmental impact of unused pharmaceuticals: Review focused on prevention. Front. Environ. Sci., 10. [DOI]
  84. 84 Samadi, 2021, Development of remediation technologies for organic contaminants informed by QSAR/QSPR models [DOI]
  85. 85 Majee, S., Sarav, M., Banik, B.K., and Ray, D. (2023). Recent Advances in the Green Synthesis of Active N-Heterocycles and Their Biological Activities. Pharmaceuticals, 16. [DOI]
  86. 86 Martins, 2015, Heterocyclic anticancer compounds: Recent advances and the paradigm shift towards the use of nanomedicine’s tool Box [DOI]
  87. 87 Sá, H., Michelin, M., Tavares, T., and Silva, B. (2022). Current Challenges for Biological Treatment of Pharmaceutical-Based Contaminants with Oxidoreductase Enzymes: Immobilization Processes, Real Aqueous Matrices and Hybrid Techniques. Biomolecules, 12. [DOI]
  88. 88 Aliste, 2023, Removal of Contaminants of Emerging Concern from a Wastewater Effluent by Solar-Driven Heterogeneous Photocatalysis: A Case Study of Pharmaceuticals [DOI]
  89. 89 Friedmann, D. (2022). A General Overview of Heterogeneous Photocatalysis as a Remediation Technology for Wastewaters Containing Pharmaceutical Compounds. Water, 14. [DOI]
  90. 90 Rout, 2021, Treatment technologies for emerging contaminants in wastewater treatment plants: A review [DOI]
  91. 91 Zhang, 2023, Toxicity evolution and control for the UV/H2O2 degradation of nitrogen-containing heterocyclic compounds: SDZ and PMM [DOI]
  92. 92 Li, 2018, Removal of indomethacin using UV–vis/peroxydisulfate: Kinetics, toxicity, and transformation pathways [DOI]
  93. 93 Jia, 2023, Construction of ACNF/Polypyrrole/MIL-100-Fe composites with exceptional removal performance for ceftriaxone and indomethacin inspired by “Ecological Infiltration System” [DOI]
  94. 94 Verliefde, 2009, Influence of membrane fouling by (pretreated) surface water on rejection of pharmaceutically active compounds (PhACs) by nanofiltration membranes [DOI]
  95. 95 Kujawska, 2022, Comparative analysis of separation methods used for the elimination of pharmaceuticals and personal care products (PPCPs) from water—A critical review [DOI]
  96. 96 Wang, 2024, Photochemical fate of β-blocker pindolol in riverine and its downstream coastal waters [DOI]
  97. 97 Raji, 2020, Efficiency evaluation of the photocatalytic degradation of telmisartan anti-hypertensive drug with Fenton, photo-Fenton and recyclable TiO2 heterogeneous catalyst [DOI]
  98. 98 Ljubas, 2018, Albendazole Degradation Possibilities by UV-Based Advanced Oxidation Processes [DOI]
  99. 99 Fukuda, 2023, Detoxification of the post-harvest antifungal pesticide thiabendazole by cold atmospheric plasma [DOI]
  100. 100 Zizzamia, 2024, Efficient photooxidation processes for the removal of sildenafil from aqueous environments: A comparative study [DOI]
  101. 101 2023, Role of the hydrolytic-acidogenic phase on the removal of bisphenol A and sildenafil during anaerobic treatment [DOI]
  102. 102 Pardo, 2018, Photochemical, thermal, biological and long-term degradation of celecoxib in river water. Degradation products and adsorption to sediment [DOI]
  103. 103 Reddy, 2024, Enhanced removal efficiency of Tetradesmus obliquus for nevirapine removal via co-substrate supplementation: Removal mechanisms, relative gene expression and metabolomics [DOI]
  104. 104 Mapetla, 2022, Biosynthesis of iron oxide nanoparticles for the degradation of methylene blue dye, sulfisoxazole antibiotic and removal of bacteria from real water [DOI]
  105. 105 Yang, 2023, Biological conversion of sulfisoxazole in an autotrophic hydrogen-based membrane biofilm reactor [DOI]
  106. 106 Giraldo, 2015, Degradation of the antibiotic oxacillin in water by anodic oxidation with Ti/IrO2 anodes: Evaluation of degradation routes, organic by-products and effects of water matrix components [DOI]
  107. 107 Regulska, 2012, Photocatalytic degradation of olanzapine in aqueous and river waters suspension of titanium dioxide [DOI]
  108. 108 Fedeila, 2023, Biodegradation of clopidogrel bisulfate by Pseudomonas aeruginosa and Pseudomonas putida strains isolated from Algerian wastewater [DOI]
  109. 109 Mansour, D., Alblawi, E., Alsukaibi, A.K.D., Humaidi, J., Tahraoui, H., Shatat, M., Teka, S., Maisara, S., Bellakhal, N., and Binous, H. (2024). Modeling and Optimization of Electrochemical Advanced Oxidation of Clopidogrel Using the Doehlert Experimental Design Combined with an Improved Grey Wolf Algorithm. Water, 16. [DOI]
  110. 110 Baaloudj, 2022, High efficient Cefixime removal from water by the sillenite Bi12TiO20: Photocatalytic mechanism and degradation pathway [DOI]
  111. 111 Aziz, 2022, High thiabendazole fungicide uptake using Cellana tramoserica shells modified by copper: Characterization, adsorption mechanism, and optimization using CCD-RSM approach [DOI]
  112. 112 Hojamberdiev, 2023, Unveiling the origin of the efficient photocatalytic degradation of nitazoxanide over bismuth (oxy)iodide crystalline phases [DOI]

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