Oxidative, Genotoxic and Cytotoxic Damage Potential of Novel Borenium and Borinium Compounds

In this study, the biological properties of novel borenium and borinium compounds in terms of their oxidative, genotoxic, and cytotoxic effects were assessed on cultured human peripheral blood cells, as well as several types of cancer cells. Our results revealed that the borinium compounds yielded the best results in terms of supporting total antioxidant capacity (TAC). In fact, borenium 1, borenium 2, borenium 3, borinium 4, and borinium 5 compounds elevated TAC levels of cultured human blood cells at rates of 42.8%, 101.5%, 69.8%, 33.3%, and 49.2%, respectively. There were no statistically significant differences (p > 0.05) between the negative control and the groups treated with all borinium and borenium concentrations from the micronucleus (MN) and chromosome aberration (CA) assays, demonstrating the non-genotoxic effects. Moreover, borenium 1 (60.7% and 50.7%), borenium 2 (70.4% and 57.2%), borenium 3 (53.1% and 45.2%), borinium 4 (55.1% and 48.1%), and borinium 5 (51.0% and 36.1%) minimized the mitomycin C(MMC)-induced genotoxic damages at different rates as determined using CA and MN assays, respectively. Again, it was found that the borinium compounds exhibited higher cytotoxic activity on cancer cells when compared to borenium compounds. Consequently, in light of our in vitro findings, it was suggested that the novel borinium and borenium compounds could be used safely in pharmacology, cosmetics, and various medical fields due to their antioxidant and non-genotoxic features, as well as their cytotoxicity potential on cancer cells.

[1]  Ivana Carev,et al.  Chemical Composition and Biological Activity of Salvia officinalis L. Essential Oil , 2023, Plants.

[2]  F. Kar,et al.  Borax regulates iron chaperone‐ and autophagy‐mediated ferroptosis pathway in glioblastoma cells , 2023, Environmental toxicology.

[3]  Shao-yong Zhang,et al.  Exploring boron applications in modern agriculture: anti-fungal activities and mechanisms of phenylboric acid derivatives. , 2023, Pest management science.

[4]  A. Basiri,et al.  A Comparison of Boron Supplement and Tamsulosin as Medical Expulsive Therapy for Urinary Stones After Extracorporeal Shock Wave Lithotripsy: a Randomized Controlled Clinical Trial , 2023, Biological Trace Element Research.

[5]  Y. Hseu,et al.  The in vitro and in vivo anticancer activities of Antrodia salmonea through inhibition of metastasis and induction of ROS-mediated apoptotic and autophagic cell death in human glioblastoma cells. , 2023, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[6]  Y. Chuang,et al.  Therapeutic Efficacy and Radiobiological Effects of Boric-Acid-Mediated BNCT in an Osteosarcoma-Bearing SD Rat Model , 2023, Life.

[7]  Wen Zhang,et al.  Design and discovery of novel dipeptide boronic acid ester proteasome inhibitors, an oral slowly-released prodrug for the treatment of multiple myeloma. , 2023, European journal of medicinal chemistry.

[8]  Tetsuro Tanaka,et al.  A Novel Amphotericin B Hydrogel Composed of Poly(Vinyl Alcohol)/Borate Complex for Ophthalmic Formulation. , 2023, Chemical & pharmaceutical bulletin.

[9]  A. Mardinoğlu,et al.  Lipoic Acid Conjugated Boron Hybrids Enhance Wound Healing and Antimicrobial Processes , 2022, Pharmaceutics.

[10]  S. Piaggi,et al.  Enhancement of ferroptosis by boric acid and its potential use as chemosensitizer in anticancer chemotherapy , 2022, BioFactors.

[11]  Dongwei Kang,et al.  Identification of Boronate-Containing Diarylpyrimidine Derivatives as Novel HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors , 2022, Molecules.

[12]  Z. Yuksekdag,et al.  In vitro genotoxic and antigenotoxic effects of an exopolysaccharide isolated from Lactobacillus salivarius KC27L. , 2022, Toxicology in vitro : an international journal published in association with BIBRA.

[13]  Ying Zhang,et al.  Design and synthesis of boron-containing ALK inhibitor with favorable in vivo efficacy. , 2022, Bioorganic & medicinal chemistry.

[14]  F. Kar,et al.  The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways , 2022, Environmental toxicology.

[15]  S. Yaşar,et al.  Investigation of the pharmacological, behavioral, and biochemical effects of boron in parkinson-indicated rats. , 2022, Cellular and molecular biology.

[16]  T. Özgürtaş,et al.  Cytotoxic and Apoptotic Effects of the Combination of Borax (Sodium Tetraborate) and 5-Fluorouracil on DLD-1 Human Colorectal Adenocarcinoma Cell Line. , 2022, Turkish journal of pharmaceutical sciences.

[17]  C. Jun,et al.  Boron attenuated diethylnitrosamine induced hepatocellular carcinoma in C3H/HeN mice via alteration of oxidative stress and apoptotic pathway. , 2022, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[18]  S. Benner,et al.  New Insights into Boron Essentiality in Humans and Animals , 2022, International journal of molecular sciences.

[19]  A. Mardinoğlu,et al.  Boron Compounds Exhibit Protective Effects against Aluminum-Induced Neurotoxicity and Genotoxicity: In Vitro and In Vivo Study , 2022, Toxics.

[20]  E. Göker,et al.  Boric acid exert anti-cancer effect in poorly differentiated hepatocellular carcinoma cells via inhibition of AKT signaling pathway. , 2022, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[21]  L. Rendina,et al.  Carboranes in drug discovery, chemical biology and molecular imaging , 2022, Nature Reviews Chemistry.

[22]  N. Kuznetsov,et al.  New type of RNA virus replication inhibitor based on decahydro-closo-decaborate anion containing amino acid ester pendant group , 2022, JBIC Journal of Biological Inorganic Chemistry.

[23]  A. Mardinoğlu,et al.  Molecular Genetics and Cytotoxic Responses to Titanium Diboride and Zinc Borate Nanoparticles on Cultured Human Primary Alveolar Epithelial Cells , 2022, Materials.

[24]  H. Tekeli,et al.  Anti- inflammatory effect of boric acid on cytokines in ovariectomy-induced rats. , 2022, Cellular and molecular biology.

[25]  F. Şahin,et al.  Anti-cancer effect of boron derivatives on small-cell lung cancer. , 2022, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[26]  A. Di Rienzo,et al.  Boron-based hybrids as novel scaffolds for the development of drugs with neuroprotective properties. , 2021, RSC medicinal chemistry.

[27]  A. Mardinoğlu,et al.  Safety and Efficacy Assessments to Take Antioxidants in Glioblastoma Therapy: From In Vitro Experiences to Animal and Clinical Studies , 2021, Neurochemistry International.

[28]  E. Sahin,et al.  Cardiac Hypertrophy Caused by Hyperthyroidism in Rats: Role of ATF-6 and TRPC1 Channels. , 2021, Canadian journal of physiology and pharmacology.

[29]  A. Mardinoğlu,et al.  Promising potential of boron compounds against Glioblastoma: In Vitro antioxidant, anti-inflammatory and anticancer studies , 2021, Neurochemistry International.

[30]  N. Hosmane,et al.  Organoboron Compounds: Effective Antibacterial and Antiparasitic Agents , 2021, Molecules.

[31]  P. Kesharwani,et al.  Recent update on potential cytotoxicity, biocompatibility and preventive measures of biomaterials used in dentistry. , 2021, Biomaterials science.

[32]  Mariusz Uchman,et al.  Boron cluster compounds as new chemical leads for antimicrobial therapy , 2021 .

[33]  A. Arslantaş,et al.  Cytotoxic Effect Of Boron Application On Glioblastoma Cells. , 2020, Turkish neurosurgery.

[34]  I. Elmaci,et al.  Boron’s neurophysiological effects and tumoricidal activity on glioblastoma cells with implications for clinical treatment , 2019, The International journal of neuroscience.

[35]  Umit Cakir,et al.  In vitro cytotoxic and genotoxic effects of newly synthesised boron ionic liquids , 2019, Biotechnology & Biotechnological Equipment.

[36]  I. Kucukkurt,et al.  Boron ameliorates arsenic‐induced DNA damage, proinflammatory cytokine gene expressions, oxidant/antioxidant status, and biochemical parameters in rats , 2018, Journal of biochemical and molecular toxicology.

[37]  Kristin E. Yamada,et al.  Boric Acid Activation of eIF2α and Nrf2 Is PERK Dependent: a Mechanism that Explains How Boron Prevents DNA Damage and Enhances Antioxidant Status , 2018, Biological Trace Element Research.

[38]  R. Marcos,et al.  Antigenotoxic potential of boron nitride nanotubes , 2018, Nanotoxicology.

[39]  B. E. Tepedelen,et al.  Boric Acid Reduces the Formation of DNA Double Strand Breaks and Accelerates Wound Healing Process , 2016, Biological Trace Element Research.

[40]  U. Sezer,et al.  Evaluation of genotoxic and antigenotoxic effects of boron by the somatic mutation and recombination test (SMART) on Drosophila , 2016, Drug and chemical toxicology.

[41]  James H. Davis,et al.  (Keynote) Boronium Based Ionic Liquids: Salts of Boron Centered Cations as Promising Salts for Electrochemical Applications , 2013 .

[42]  A. Prokofjevs,et al.  Borenium ion catalyzed hydroboration of alkenes with N-heterocyclic carbene-boranes. , 2012, Journal of the American Chemical Society.

[43]  M. Lavin,et al.  ATM Activation by Oxidative Stress , 2010, Science.

[44]  I. Kucukkurt,et al.  The effects of dietary boric acid and borax supplementation on lipid peroxidation, antioxidant activity, and DNA damage in rats. , 2010, Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements.

[45]  A. Hollenkamp,et al.  Stable Cycling of Lithium Batteries Using Novel Boronium-Cation-Based Ionic Liquid Electrolytes† , 2010 .

[46]  Yi Xia,et al.  Therapeutic potential of boron-containing compounds. , 2009, Future medicinal chemistry.

[47]  Kimberly Henderson,et al.  Receptor Activated Ca2+ Release Is Inhibited by Boric Acid in Prostate Cancer Cells , 2009, PloS one.

[48]  R. Kowalski,et al.  DNA cross-linking, double-strand breaks, and apoptosis in corneal endothelial cells after a single exposure to mitomycin C. , 2008, Investigative ophthalmology & visual science.

[49]  A. Tatar,et al.  Effects of Some Boron Compounds on Peripheral Human Blood , 2007, Zeitschrift fur Naturforschung. C, Journal of biosciences.

[50]  S. Bakırdere,et al.  Effects of dietary boron on cervical cytopathology and on micronucleus frequency in exfoliated buccal cells , 2007, Environmental toxicology.

[51]  Shakir Ali,et al.  Boron ameliorates fulminant hepatic failure by counteracting the changes associated with the oxidative stress. , 2006, Chemico-biological interactions.

[52]  C. Eckhert,et al.  Cellular changes in boric acid-treated DU-145 prostate cancer cells , 2006, British Journal of Cancer.

[53]  K. Jamil,et al.  Cytotoxicity and Genotoxicity Induced by the Pesticide Profenofos on Cultured Human Peripheral Blood Lymphocytes , 2006, Drug and chemical toxicology.

[54]  W. Piers,et al.  Borinium, borenium, and boronium ions: synthesis, reactivity, and applications. , 2005, Angewandte Chemie.

[55]  A. Wierzbicki,et al.  Exploiting isolobal relationships to create new ionic liquids: novel room-temperature ionic liquids based upon (N-alkylimidazole)(amine)BH2+"boronium" ions. , 2005, Chemical communications.

[56]  C. Eckhert,et al.  Boric acid inhibits human prostate cancer cell proliferation. , 2004, Cancer letters.

[57]  S. Muallem,et al.  NaBC1 is a ubiquitous electrogenic Na+ -coupled borate transporter essential for cellular boron homeostasis and cell growth and proliferation. , 2004, Molecular cell.

[58]  R. Maronpot,et al.  Boron Supplementation Inhibits the Growth and Local Expression of IGF-1 in Human Prostate Adenocarcinoma (LNCaP) Tumors in Nude Mice , 2004, Toxicologic pathology.

[59]  M. Fenech,et al.  HUMN project: detailed description of the scoring criteria for the cytokinesis-block micronucleus assay using isolated human lymphocyte cultures. , 2003, Mutation research.

[60]  J. Beijnen,et al.  CRC/EORTC/NCI Joint Formulation Working Party: experiences in the formulation of investigational cytotoxic drugs. , 1995, British Journal of Cancer.

[61]  R. Chapin,et al.  Tissue disposition of boron in male Fischer rats. , 1991, Toxicology and applied pharmacology.

[62]  K. Ohta [Basic Organic and Inorganic Chemistry of Boron Clusters and Its Application to Drug Discovery]. , 2023, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[63]  Meng Lei,et al.  Design, synthesis, in vitro and in vivo evaluation, and structure-activity relationship (SAR) discussion of novel dipeptidyl boronic acid proteasome inhibitors as orally available anti-cancer agents for the treatment of multiple myeloma and mechanism studies. , 2018, Bioorganic & medicinal chemistry.

[64]  A. Tatar,et al.  The effects of some boron compounds against heavy metal toxicity in human blood. , 2012, Experimental and toxicologic pathology : official journal of the Gesellschaft fur Toxikologische Pathologie.

[65]  J. Beijnen,et al.  EORTC/CRC/NCI guidelines for the formulation of investigational cytotoxic drugs. , 1988, European journal of cancer & clinical oncology.