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Review Article

Organoboronic acids/esters as effective drug and prodrug candidates in cancer treatments: challenge and hope

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Article: 2220084 | Received 10 Jan 2023, Accepted 26 May 2023, Published online: 15 Jun 2023

References

  • Watanabe T, Momose I. [Boronic acid as a promising class of chemical entity for development of clinical medicine for targeted therapy of cancer]. Yakugaku Zasshi. 2022;142(2):145–153.
  • (a) Sun X, Peng Y, Zhao J, Xie Z, Lei X, Tang G. Discovery and development of tumor glycolysis rate-limiting enzyme inhibitors. Bioorg Chem. 2021;112:104891. (b)Zolghadri S, Bahrami A, Hassan Khan MT, Munoz-Munoz J, Garcia-Molina F, Garcia-Canovas F, Saboury AA. A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem. 2019;34(1):279–309. (c)Lin H, Li Q, Li Q, Zhu J, Gu K, Jiang X, Hu Q, Feng F, Qu W, Chen Y, et al. Small molecule KDM4s inhibitors as anti-cancer agents. J Enzyme Inhib Med Chem. 2018;33(1):777–793. (d)Supuran CT. Anti-obesity carbonic anhydrase inhibitors: challenges and opportunities. J Enzyme Inhib Med Chem. 2022;37(1):2478–2488.
  • (a) Schwarzel WC, Kruggel WG, Brodie HJ. Studies on the mechanism of estrogen biosynthesis. 8. The development of inhibitors of the enzyme system in human placenta. Endocrinology. 1973;92(3):866–880. (b)Siiteri PK, Thompson EA. Studies of human placental aromatase. J Steroid Biochem. 1975;6(3-4):317–322. (c) Brueggemeier RW, Floyd EE, Counsell RE. Synthesis and biochemical evaluation of inhibitors of estrogen biosynthesis. J Med Chem. 1978;21(10):1007–1011.
  • (a) Lacal PM, Graziani G. Therapeutic implication of vascular endothelial growth factor receptor-1 (VEGFR-1) targeting in cancer cells and tumor microenvironment by competitive and non-competitive inhibitors. Pharmacol Res. 2018;136:97–107. (b) Zhang Q, Miao YH, Liu T, Yun YL, Sun XY, Yang T, Sun J. Natural source, bioactivity and synthesis of 3-arylcoumarin derivatives. J Enzyme Inhib Med Chem. 2022;37(1):1023–1042.
  • McClure JJ, Li X, Chou CJ. Advances and challenges of HDAC inhibitors in cancer therapeutics. Adv Cancer Res. 2018;138:183–211.
  • Zhang L, Zhang J, Jiang Q, Zhang L, Song W. Zinc binding groups for histone deacetylase inhibitors. J Enzyme Inhib Med Chem. 2018;33(1):714–721.
  • Hunt CD. Dietary boron: progress in establishing essential roles in human physiology. J Trace Elem Med Biol. 2012;26(2-3):157–160.
  • Pizzorno L. Nothing boring about boron. Integr Med. 2015;14(4):35–48.
  • Ying X, Cheng S, Wang W, Lin Z, Chen Q, Zhang W, Kou D, Shen Y, Cheng X, Rompis FA, et al. Effect of boron on osteogenic differentiation of human bone marrow stromal cells. Biol Trace Elem Res. 2011;144(1-3):306–315.
  • (a) Hall DG. Structure, properties, and preparation of boronic acid derivatives. In: Hall DG, editor. Boronic acids. Wiley‐VCH Verlag GmbH & Co. KGaA; 2011. p. 1–133. (b) Hosmane NSE. Boron science: new technologies and applications. 1st ed. Boca Raton (FL): CRC Press; 2012. (c) Hosmane NS, Eagling R. Handbook of boron science. Singapore: World Scientific; 2018. doi:10.1142/q0130-vol4. (d) Hey-Hawkins TE, editor. Boron-based compounds: potential and emerging applications in medicine. Pharm Med Chem 2018;1:3–109.
  • Fernandes GFS, Denny WA, Dos Santos JL. Boron in drug design: recent advances in the development of new therapeutic agents. Eur J Med Chem. 2019;179:791–804.
  • Tanaka K. The proteasome: overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci. 2009;85(1):12–36.
  • Gonzalez A, Peters U, Lampe JW, White E. Boron intake and prostate cancer risk. Cancer Causes Control. 2007;18(10):1131–1140.
  • Scorei RI, Popa R. Jr. Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anticancer Agents Med Chem. 2010;10(4):346–351.
  • (a) António JPM, Russo R, Carvalho CP, Cal P, Gois PMP. Boronic acids as building blocks for the construction of therapeutically useful bioconjugates. Chem Soc Rev. 2019;48(13):3513–3536. (b) Ye H, Zhou Y, Liu X, Chen Y, Duan S, Zhu R, Liu Y, Yin L. Recent advances on reactive oxygen species-responsive delivery and diagnosis system. Biomacromolecules. 2019;20(7):2441–2463.
  • Peiró Cadahía J, Previtali V, Troelsen NS, Clausen MH. Prodrug strategies for targeted therapy triggered by reactive oxygen species. Medchemcomm. 2019;10(9):1531–1549.
  • Andina D, Leroux JC, Luciani P. Ratiometric fluorescent probes for the detection of reactive oxygen species. Chemistry. 2017;23(55):13549–13573.
  • Peng X, Gandhi V. ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage. Ther Deliv. 2012;3(7):823–833.
  • Cao S, Christiansen R, Peng X. Substituent effects on oxidation-induced formation of quinone methides from arylboronic ester precursors. Chemistry. 2013;19(27):9050–9058.
  • Zielonka J, Sikora A, Hardy M, Joseph J, Dranka BP, Kalyanaraman B. Boronate probes as diagnostic tools for real time monitoring of peroxynitrite and hydroperoxides. Chem Res Toxicol. 2012;25(9):1793–1799.
  • (a) Sikora A, Zielonka J, Lopez M, Joseph J, Kalyanaraman B. Direct oxidation of boronates by peroxynitrite: mechanism and implications in fluorescence imaging of peroxynitrite. Free Radic Biol Med. 2009;47(10):1401–1407. (b) Sikora A, Zielonka J, Lopez M, Dybala-Defratyka A, Joseph J, Marcinek A, Kalyanaraman B. Reaction between peroxynitrite and boronates: EPR spin-trapping, HPLC analyses, and quantum mechanical study of the free radical pathway. Chem Res Toxicol. 2011;24(5):687–697.
  • Dong C, Zhou Q, Xiang J, Liu F, Zhou Z, Shen Y. Self-assembly of oxidation-responsive polyethylene glycol-paclitaxel prodrug for cancer chemotherapy. J Control Release. 2020;321:529–539.
  • Hanna RD, Naro Y, Deiters A, Floreancig PE. Alcohol, aldehyde, and ketone liberation and intracellular cargo release through peroxide-mediated α-boryl ether fragmentation. J Am Chem Soc. 2016;138(40):13353–13360.
  • (a) Mosey RA, Floreancig PE. Versatile approach to α-alkoxy carbamate synthesis and stimulus-responsive alcohol release. Org Biomol Chem. 2012;10(39):7980–7985. (b) Brooks AD, Mohapatra H, Phillips ST. Design, synthesis, and characterization of small-molecule reagents that cooperatively provide dual readouts for triaging and, when necessary, quantifying point-of-need enzyme assays. J Org Chem. 2015;80(21):10437–10445.
  • Efremenko Y, Mirsky VM. 3-Thienylboronic acid as a receptor for diol-containing compounds: a study by isothermal titration calorimetry. Chemosensors. 2022;10(7):251.
  • (a) Liu J, Zheng S, Akerstrom VL, Yuan C, Ma Y, Zhong Q, Zhang C, Zhang Q, Guo S, Ma P, et al. Fulvestrant-3 boronic acid (ZB716): an orally bioavailable selective estrogen receptor downregulator (SERD). J Med Chem. 2016;59(17):8134–8140. (b) Kar F, Hacioglu C, Senturk H, Donmez DB, Kanbak G. The role of oxidative stress, renal inflammation, and apoptosis in post ischemic reperfusion injury of kidney tissue: the protective effect of dose-dependent boric acid administration. Biol Trace Elem Res. 2020;195(1):150–158. (c) Kar F, Hacıoğlu C, Göncü Y, Söğüt İ, Şenturk H, Burukoğlu Dönmez D, Kanbak G, Ay N. In vivo assessment of the effect of hexagonal boron nitride nanoparticles on biochemical, histopathological, oxidant and antioxidant status. J Clust Sci. 2021;32(2):517–529.
  • (a) Alouane A, Labruère R, Le Saux T, Schmidt F, Jullien L. Self-immolative spacers: kinetic aspects, structure-property relationships, and applications. Angew Chem Int Ed Engl. 2015;54(26):7492–7509. (b) Gisbert-Garzarán M, Manzano M, Vallet-Regí M. Self-immolative chemistry in nanomedicine. Chem Eng J. 2018;340:24–31.
  • (a) Baker SJ, Ding CZ, Akama T, Zhang YK, Hernandez V, Xia Y. Therapeutic potential of boron-containing compounds. Future Med Chem. 2009;1(7):1275–1288. (b) Ciani L, Ristori S. Boron as a platform for new drug design. Expert Opin Drug Discov. 2012;7(11):1017–1027. (c) Das BC, Thapa P, Karki R, Schinke C, Das S, Kambhampati S, Banerjee SK, Van Veldhuizen P, Verma A, Weiss LM, et al. Boron chemicals in diagnosis and therapeutics. Future Med Chem. 2013;5(6):653–676. (d) Messner K, Vuong B, Tranmer GK. The boron advantage: the evolution and diversification of boron’s applications in medicinal chemistry. Pharmaceuticals. 2022;15(3):264. (e) Stefaniak J, Nowak MG, Wojciechowski M, Milewski S, Skwarecki AS. Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics - synthesis and properties. J Enzyme Inhib Med Chem. 2022;37(1):1928–1956.
  • (a) Brown HC, Malhotra SV, Ramachandran PV. Organoboranes for synthesis 17. Generality of hydroboration-amination for the conversion of terpenes into enantiomerically pure terpenylamines. Their utility for gas chromatographic analysis of chiral carboxylic acids. Tetrahedron Asymmetry. 1996;7(12):3527–3534. (b) Cid J, Carbó JJ, Fernández E. Disclosing the structure/activity correlation in trivalent boron-containing compounds: a tendency map. Chemistry. 2012;18(40):12794–12802. (c) Hosmane, NS. Future perspectives for boron and gadolinium neutron capture therapies in cancer treatment. In: Hosmane NS, editor. Boron and gadolinium neutron capture therapy for cancer treatment. Singapore: World Scientific; 2011. p. 165–170.
  • (a) Al-Zoubi RM, Al-Jammal WK, McDonald R. Regioselective synthesis of ortho-iodobiphenylboronic acid derivatives: a superior catalyst for carboxylic acid activation. New J Chem. 2020;44(9):3612–3623. (b) Austin B. Novel pharmaceutical compounds from marine bacteria. J Appl Bacteriol. 1989;67(5):461–470. (c) Chen X, Schauder S, Potier N, Van Dorsselaer A, Pelczer I, Bassler BL, Hughson FM. Structural identification of a bacterial quorum-sensing signal containing boron. Nature. 2002;415(6871):545–549. (d)Gademann K, Portmann C. Secondary metabolites from cyanobacteria: complex structures and powerful bioactivities. Curr Org Chem. 2008;12(4):326–341. (e) Irschik H, Schummer D, Gerth K, Höfle G, Reichenbach H. The tartrolons, new boron-containing antibiotics from a myxobacterium, Sorangium cellulosum. J Antibiot. 1995;48(1):26–30. (f) Al-Zoubi RM, Al-Zoubi MS, Abazid AH, McDonald R. Terminal versus internal diiodobenzyl alcohol derivatives via regioselective metal-iodine exchange of 1,2,3-triiodoarenes: synthesis and antibacterial activity. Asian J Org Chem. 2015;4(4):359–367. (g) Al-Zoubi RM, Ibdah A, Al-Jammal WK, Al-Zoubi MS, Almasalma AA, McDonald R. Mild, efficient, and regioselective synthesis of diiodophenyl-boronic acid derivatives via metal-iodine exchange of 5-substituted 1,2,3-triiodoarenes. Synthesis. 2018;50(02):384–390.
  • Baldock C, de Boer GJ, Rafferty JB, Stuitje AR, Rice DW. Mechanism of action of diazaborines. Biochem Pharmacol. 1998;55(10):1541–1549.
  • Jabbour A, Steinberg D, Dembitsky VM, Moussaieff A, Zaks B, Srebnik M. Synthesis and evaluation of oxazaborolidines for antibacterial activity against Streptococcus mutans. J Med Chem. 2004;47(10):2409–2410.
  • Benkovic SJ, Baker SJ, Alley MRK, Woo Y-H, Zhang Y-K, Akama T, Mao W, Baboval J, Rajagopalan PTR, Wall M, et al. Identification of borinic esters as inhibitors of bacterial cell growth and bacterial methyltransferases, CcrM and MenH. J Med Chem. 2005;48(23):7468–7476.
  • Baker SJ, Zhang YK, Akama T, Lau A, Zhou H, Hernandez V, Mao W, Alley MR, Sanders V, Plattner JJ. Discovery of a new boron-containing antifungal agent, 5-fluoro-1,3-dihydro-1-hydroxy-2,1- benzoxaborole (AN2690), for the potential treatment of onychomycosis. J Med Chem. 2006;49(15):4447–4450.
  • Al-Zoubi RM, Al-Zoubi MS, Jaradat KT, McDonald R. Design, synthesis and X-ray crystal structure of iodinated benzoboroxole derivatives by consecutive metal–iodine exchange of 3,4,5-triiodoanisole. Eur J Org Chem. 2017;2017(38):5800–5808.
  • Akama T, Baker SJ, Zhang YK, Hernandez V, Zhou H, Sanders V, Freund Y, Kimura R, Maples KR, Plattner JJ. Discovery and structure-activity study of a novel benzoxaborole anti-inflammatory agent (AN2728) for the potential topical treatment of psoriasis and atopic dermatitis. Bioorg Med Chem Lett. 2009;19(8):2129–2132.
  • Dogan EE. Computational bioactivity analysis and bioisosteric investigation of the approved breast cancer drugs proposed new design drug compounds: increased bioactivity coming with silicon and boron. Lett Drug Des Discov. 2021;18(6):551–561.
  • Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 2019;144(8):1941–1953.
  • Kuczynski EA, Sargent DJ, Grothey A, Kerbel RS. Drug rechallenge and treatment beyond progression–implications for drug resistance. Nat Rev Clin Oncol. 2013;10(10):571–587.
  • U.S. Food and Drug Administration. Drug approval package. Maryland: FDA; 2003.
  • Ortho Biotech - Division of Janssen-Ortho Inc. VELCADE for multiple myeloma receives front-line approval in Canada. Canada: Johnson and Johnson; 2008.
  • (a) Adams J. The development of proteasome inhibitors as anticancer drugs. Cancer Cell. 2004;5(5):417–421. (b) Arkwright R, Pham TM, Zonder JA, Dou QP. The preclinical discovery and development of bortezomib for the treatment of mantle cell lymphoma. Expert Opin Drug Discov. 2017;12(2):225–235.
  • Chen D, Frezza M, Schmitt S, Kanwar J, Dou QP. Bortezomib as the first proteasome inhibitor anticancer drug: current status and future perspectives. Curr Cancer Drug Targets. 2011;11(3):239–253.
  • Williams C, Luis M, Lopez I, Coca A. The chemistry of organoboron species: classification and basic properties. In: Gandelman M, Marek I, editors. PATAI’s chemistry of functional groups. Delaware: John Wiley & Sons; 2021. p. 1–21.
  • Bross PF, Kane R, Farrell AT, Abraham S, Benson K, Brower ME, Bradley S, Gobburu JV, Goheer A, Lee SL, et al. Approval summary for bortezomib for injection in the treatment of multiple myeloma. Clin Cancer Res. 2004;10(12 Pt 1):3954–3964.
  • Shirley M. Ixazomib: first global approval. Drugs. 2016;76(3):405–411.
  • Takeda Pharmaceutical Company Ltd. Health Canada approves Ninlaro (ixazomib) for use in relapsed/refractory multiple myeloma. Ontario (CA): International Myeloma Foundation; 2016.
  • Muz B, Ghazarian RN, Ou M, Luderer MJ, Kusdono HD, Azab AK. Spotlight on ixazomib: Potential in the treatment of multiple myeloma (Review). Drug Des Devel Ther. 2016;10:217–226.
  • Kupperman E, Lee EC, Cao Y, Bannerman B, Fitzgerald M, Berger A, Yu J, Yang Y, Hales P, Bruzzese F, et al. Evaluation of the proteasome inhibitor MLN9708 in preclinical models of human cancer. Cancer Res. 2010;70(5):1970–1980.
  • Dick LR, Fleming PE. Building on bortezomib: second-generation proteasome inhibitors as anti-cancer therapy. Drug Discov Today. 2010;15(5-6):243–249.
  • (a) Dimopoulos MA, Grosicki S, Jędrzejczak WW, Nahi H, Gruber A, Hansson M, Gupta N, Byrne C, Labotka R, Teng Z, et al. All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Eur J Cancer. 2019;106:89–98. (b) Gupta N, Hanley MJ, Harvey RD, Badros A, Lipe B, Kukreti V, Berdeja J, Yang H, Hui AM, Qian M, et al. A pharmacokinetics and safety phase 1/1b study of oral ixazomib in patients with multiple myeloma and severe renal impairment or end-stage renal disease requiring haemodialysis. Br J Haematol. 2016;174(5):748–759.
  • Gupta N, Yang H, Hanley MJ, Zhang S, Liu R, Kumar S, Richardson PG, Skacel T, Venkatakrishnan K. Dose and schedule selection of the oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma: clinical and model-based analyses. Target Oncol. 2017;12(5):643–654.
  • Ludwig H, Avet-Loiseau H, Bladé J, Boccadoro M, Cavenagh J, Cavo M, Davies F, de la Rubia J, Delimpasi S, Dimopoulos M, et al. European perspective on multiple myeloma treatment strategies: update following recent congresses. Oncologist. 2012;17(5):592–606.
  • US Food and Drug Administration. FDA drug approval process infographic. USA: Food and Drug Administration; 2014.
  • Hughes JP, Rees S, Kalindjian SB, Philpott KL. Principles of early drug discovery. Br J Pharmacol. 2011;162(6):1239–1249.
  • Bhat V, Chatterjee J. The use of in silico tools for the toxicity prediction of potential inhibitors of SARS-CoV-2. Altern Lab Anim. 2021;49(1-2):22–32.
  • Cengiz Seval G, Beksac M. The safety of bortezomib for the treatment of multiple myeloma. Expert Opin Drug Saf. 2018;17(9):953–962.
  • VELCADE. Prescribing information. Ontario (CA): Takeda Pharmaceuticals America; 2022.
  • BORTEZOMIB FOR INJECTION. Bortezomib for Injection. Toronto (CA): Teva Canada Limited; 2006.
  • Jouni H, Aubry MC, Lacy MQ, Vincent Rajkumar S, Kumar SK, Frye RL, Herrmann J. Ixazomib cardiotoxicity: a possible class effect of proteasome inhibitors. Am J Hematol. 2017;92(2):220–221.
  • (a) Nguyen MN, Nayernama A, Jones SC, Kanapuru B, Gormley N, Waldron PE. Proteasome inhibitor-associated thrombotic microangiopathy: a review of cases reported to the FDA adverse event reporting system and published in the literature. Am J Hematol. 2020;95(9):E218–E222. (b) Ariely D, Lanier WL. Disturbing trends in physician burnout and satisfaction with work-life balance: dealing with malady among the nation’s healers. Mayo Clin Proc. 2015;90(12):1593–1596. (c) Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hajek R, Facon T, Ludwig H, Oriol A, Goldschmidt H, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27–38.
  • Plescia J, Moitessier N. Design and discovery of boronic acid drugs (Review). Eur J Med Chem. 2020;195:112270.
  • Cunningham CC. Talabostat. Expert Opin Investig Drugs. 2007;16(9):1459–1465.
  • Flentke GR, Munoz E, Huber BT, Plaut AG, Kettner CA, Bachovchin WW. Inhibition of dipeptidyl aminopeptidase IV (DP-IV) by Xaa-boroPro dipeptides and use of these inhibitors to examine the role of DP-IV in T-cell function. Proc Natl Acad Sci U S A. 1991;88(4):1556–1559.
  • Rashmi R, Kumar S, Karunagaran D. Ectopic expression of Bcl-XL or Ku70 protects human colon cancer cells (SW480) against curcumin-induced apoptosis while their down-regulation potentiates it. Carcinogenesis. 2004;25(10):1867–1877.
  • Offidani M, Corvatta L, Morè S, Olivieri A. Novel experimental drugs for treatment of multiple myeloma (Review). J Exp Pharmacol. 2021;13:245–264.
  • Vogl DT, Martin TG, Vij R, Hari P, Mikhael JR, Siegel D, Wu KL, Delforge M, Gasparetto C. Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leuk Lymphoma. 2017;58(8):1872–1879.
  • (a) Hatakeyama S, Ohyama C, Minagawa S, Inoue T, Kakinuma H, Kyan A, Arai Y, Suga T, Nakayama J, Kato T, et al. Functional correlation of trophinin expression with the malignancy of testicular germ cell tumor. Cancer Res. 2004;64(12):4257–4262. (b) Santo L, Hideshima T, Kung AL, Tseng JC, Tamang D, Yang M, Jarpe M, van Duzer JH, Mazitschek R, Ogier WC, et al. Preclinical activity, pharmacodynamic, and pharmacokinetic properties of a selective HDAC6 inhibitor, ACY-1215, in combination with bortezomib in multiple myeloma. Blood. 2012;119(11):2579–2589. (c) Arastu-Kapur S, Anderl JL, Kraus M, Parlati F, Shenk KD, Lee SJ, Muchamuel T, Bennett MK, Driessen C, Ball AJ, et al. Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin Cancer Res. 2011;17(9):2734–2743.
  • Han LQ, Yuan X, Wu XY, Li RD, Xu B, Cheng Q, Liu ZM, Zhou TY, An HY, Wang X, et al. Urea-containing peptide boronic acids as potent proteasome inhibitors. Eur J Med Chem. 2017;125:925–939.
  • (a) Bani-Yaseen AD. The supramolecular host-guest complexation of Vemurafenib with β-cyclodextrin and cucurbit[7]uril as drug photoprotecting systems: a DFT/TD-DFT study. Comput Theor Chem. 2020;1191:113026. (b) Bani-Yaseen AD. Investigation on the impact of solvent on the photochemical properties of the photoactive anticancer drug Vemurafenib: a computational study. J Mol Liq. 2021;322:114900. (c) Bani-Yaseen AD. Computational study on the mechanism of the photouncaging reaction of Vemurafenib: toward an enhanced photoprotection approach for photosensitive drugs. Molecules. 2021;26(7):1846. (d) Gupta N, Hanley MJ, Venkatakrishnan K, Perez R, Norris RE, Nemunaitis J, Yang H, Qian MG, Falchook G, Labotka R, et al. Pharmacokinetics of ixazomib, an oral proteasome inhibitor, in solid tumour patients with moderate or severe hepatic impairment. Br J Clin Pharmacol. 2016;82(3):728–738. (e) Wang Y, Lin B. In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease. Bone. 2013;55(1):132–149.
  • Lei M, Feng H, Bai E, Zhou H, Wang J, Qin Y, Zhang H, Wang X, Liu Z, Hai O, et al. Discovery of a novel dipeptidyl boronic acid proteasome inhibitor for the treatment of multiple myeloma and triple-negative breast cancer. Org Biomol Chem. 2019;17(3):683–691.
  • Zhou Y, Liu X, Xue J, Liu L, Liang T, Li W, Yang X, Hou X, Fang H. Discovery of peptide boronate derivatives as histone deacetylase and proteasome dual inhibitors for overcoming bortezomib resistance of multiple myeloma. J Med Chem. 2020;63(9):4701–4715.
  • Wang X, Zhang W, Wen T, Miao H, Hu W, Liu H, Lei M, Zhu Y. Design and discovery of novel dipeptide boronic acid ester proteasome inhibitors, an oral slowly-released prodrug for the treatment of multiple myeloma. Eur J Med Chem. 2023;250:115187.
  • Llona-Minguez S, Höglund A, Jacques SA, Johansson L, Calderón-Montaño JM, Claesson M, Loseva O, Valerie NCK, Lundbäck T, Piedrafita J, et al. Discovery of the first potent and selective inhibitors of human dCTP pyrophosphatase 1. J Med Chem. 2016;59(3):1140–1148.
  • Zhang J, Zhang J, Hao G, Xin W, Yang F, Zhu M, Zhou H. Design, synthesis, and structure-activity relationship of 7-propanamide benzoxaboroles as potent anticancer agents. J Med Chem. 2019;62(14):6765–6784.
  • Zhang C, Zhong Q, Zhang Q, Zheng S, Miele L, Wang G. Boronic prodrug of endoxifen as an effective hormone therapy for breast cancer. Breast Cancer Res Treat. 2015;152(2):283–291.
  • Point Therapeutics. Study of talabostat + docetaxel versus docetaxel in stage IIIB/IV non-small cell lung cancer (NSCLC) after failure of platinum-based chemotherapy. Indianapolis (Indiana): NIH, ClinicalTrials.gov; 2007.
  • Vogl DT, Martin TG, Vij R, Hari P, Mikhael JR, Siegel D, Wu KL, Delforge M, Gasparetto C. Phase I/II study of the novel proteasome inhibitor delanzomib (CEP-18770) for relapsed and refractory multiple myeloma. Leuk Lymphoma. 2017;58(8):1872–1879.
  • Mori Y, Suzuki A, Yoshino K, Kakihana H. Complex formation of p-boronophenylalanine with some monosaccharides. Pigment Cell Res. 1989;2(4):273–277.
  • Nedunchezhian K, Aswath N, Thiruppathy M, Thirugnanamurthy S. Boron neutron capture therapy - a literature review. J Clin Diagn Res. 2016;10(12):Ze01–Ze04.
  • Shimosegawa E, Isohashi K, Naka S, Horitsugi G, Hatazawa J. Assessment of (10)B concentration in boron neutron capture therapy: potential of image-guided therapy using (18)FBPA PET. Ann Nucl Med. 2016;30(10):749–755.
  • Wongthai P, Hagiwara K, Miyoshi Y, Wiriyasermkul P, Wei L, Ohgaki R, Kato I, Hamase K, Nagamori S, Kanai Y. Boronophenylalanine, a boron delivery agent for boron neutron capture therapy, is transported by ATB0,+, LAT1 and LAT2. Cancer Sci. 2015;106(3):279–286.
  • Malouff TD, Seneviratne DS, Ebner DK, Stross WC, Waddle MR, Trifiletti DM, Krishnan S. Boron neutron capture therapy: a review of clinical applications (Review). Front Oncol. 2021;11:1–11.
  • Scorei IR. Calcium fructoborate: plant-based dietary boron as potential medicine for cancer therapy. Front Biosci. 2011;3(1):205–215.
  • Scorei RI, Rotaru P. Calcium fructoborate–potential anti-inflammatory agent. Biol Trace Elem Res. 2011;143(3):1223–1238.
  • Ai Y, Obianom ON, Kuser M, Li Y, Shu Y, Xue F. Enhanced tumor selectivity of 5-fluorouracil using a reactive oxygen species-activated prodrug approach. ACS Med Chem Lett. 2019;10(1):127–131.
  • Ye M, Han Y, Tang J, Piao Y, Liu X, Zhou Z, Gao J, Rao J, Shen Y. A tumor-specific cascade amplification drug release nanoparticle for overcoming multidrug resistance in cancers. Adv Mater. 2017;29(38):1702342.
  • Pan Q, Zhang B, Peng X, Wan S, Luo K, Gao W, Pu Y, He B. A dithiocarbamate-based H2O2-responsive prodrug for combinational chemotherapy and oxidative stress amplification therapy. Chem Commun. 2019;55(92):13896–13899.
  • Kuang Y, Balakrishnan K, Gandhi V, Peng X. Hydrogen peroxide inducible DNA cross-linking agents: targeted anticancer prodrugs. J Am Chem Soc. 2011;133(48):19278–19281.
  • Bielec B, Poetsch I, Ahmed E, Heffeter P, Keppler BK, Kowol CR. Reactive oxygen species (ROS)-sensitive prodrugs of the tyrosine kinase inhibitor crizotinib. Molecules. 2020;25(5):1149.
  • Maslah H, Skarbek C, Pethe S, Labruère R. Anticancer boron-containing prodrugs responsive to oxidative stress from the tumor microenvironment. Eur J Med Chem. 2020;207:112670.
  • Kim EJ, Bhuniya S, Lee H, Kim HM, Cheong C, Maiti S, Hong KS, Kim JS. An activatable prodrug for the treatment of metastatic tumors. J Am Chem Soc. 2014;136(39):13888–13894.
  • Shimizu K, Maruyama M, Yasui Y, Minegishi H, Ban HS, Nakamura H. Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1alpha inhibitors. Bioorg Med Chem Lett. 2010;20(4):1453–1456.
  • National Health Service (NHS). Multiple myeloma. England: NHS; 2021.
  • National Comprehensive Cancer Network (NCCN). NCCN guidelines: multiple myeloma. Pennsylvania (USA): NCCN; 2013.
  • Knauf W, Abenhardt W, Aldaoud A, Nusch A, Grugel R, Münz M, Hartmann H, Marschner N, TLN Study Group. Treatment of non-transplant patients with multiple myeloma: routine treatment by office-based haematologists in Germany–data from the prospective Tumour Registry Lymphatic Neoplasms (TLN). Oncol Res Treat. 2014;37(11):635–636, 638–644.
  • (a) Kortüm MEH, Naumann R, Peest D, Liebisch P, Goldschmidt H. DGHO-leitlinie multiples myelom. Washington (DC): Blood, American Society of Hematology; 2010. (b) Kyle RA, Rajkumar SV. Multiple myeloma. Blood. 2008;111(6):2962–2972.
  • Harousseau JL, Dreyling M, ESMO Guidelines Working Group. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2010;21 Suppl 5:v155–v157.
  • Nielsen FH. Update on human health effects of boron (Review). J Trace Elem Med Biol. 2014;28(4):383–387.
  • Fujimoto T, Maekawa Y, Takao S, Hori S, Andoh T, Sakurai Y, Tanaka H, Kinashi Y, Masunaga S, Ichikawa H, et al. Anti-tumor effect of boron neutron capture therapy (BNCT) on axillary lymph node metastasis of breast cancer. KURRI Prog Rep. 2016;44:53.
  • (a) Hacioglu C, Kar F, Kar E, Kara Y, Kanbak G. Effects of curcumin and boric acid against neurodegenerative damage induced by amyloid beta (1-42). Biol Trace Elem Res. 2021;199(10):3793–3800. (b) Kar F, Hacioğlu C, Kaçar S. The dual role of boron in vitro neurotoxication of glioblastoma cells via SEMA3F/NRP2 and ferroptosis signaling pathways. Environ Toxicol. 2023;38(1):70–77. (c) Hacioglu C, Kar F, Davran F, Tuncer C. Borax regulates iron chaperone- and autophagy-mediated ferroptosis pathway in glioblastoma cells. Environ Toxicol. 2023;38:1–12.
  • Satapathy R, Dash BP, Bode BP, Byczynski EA, Hosmane SN, Bux S, Hosmane NS. New classes of carborane-appended 5-thio-D-glucopyranose derivatives. Dalton Trans. 2012;41(29):8982–8988.
  • Andoh T, Fujimoto T, Satani R, Suzuki M, Wada K, Sudo T, Sakurai Y, Tanaka H, Takata T, Ichikawa H. Preclinical study of boron neutron capture therapy for bone metastasis using human breast cancer cell lines. Appl Radiat Isot. 2020;165:109257.
  • (a) Barth RF, Coderre JA, Vicente MG, Blue TE. Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res. 2005;11(11):3987–4002. (b) Yamamoto T, Nakai K, Matsumura A. Boron neutron capture therapy for glioblastoma. Cancer Lett. 2008;262(2):143–152.
  • (a) Khaliq H, Juming Z, Ke-Mei P. The physiological role of boron on health (Review). Biol Trace Elem Res. 2018;186(1):31–51. (b) Rondanelli M, Faliva MA, Peroni G, Infantino V, Gasparri C, Iannello G, Perna S, Riva A, Petrangolini G, Tartara A. Pivotal role of boron supplementation on bone health: a narrative review (Review). J Trace Elem Med Biol. 2020;62:126577.
  • Fernandez SV, Russo J. Estrogen and xenoestrogens in breast cancer (Review). Toxicol Pathol. 2010;38(1):110–122.
  • Russo J, Russo IH. The role of estrogen in the initiation of breast cancer. J Steroid Biochem Mol Biol. 2006;102(1-5):89–96.
  • (a) Scorei R, Ciubar R, Ciofrangeanu CM, Mitran V, Cimpean A, Iordachescu D. Comparative effects of boric acid and calcium fructoborate on breast cancer cells. Biol Trace Elem Res. 2008;122(3):197–205. (b) Kisacam MA, Ambarcioglu P, Yakan A. Calcium fructoborate regulate colon cancer (Caco-2) cytotoxicity through modulation of apoptosis. J Biochem Mol Toxicol. 2022;36(5):e23021.
  • Zhang C, Guo S, Zhong Q, Zhang Q, Hossain A, Zheng S, Wang G. Metabolism and pharmacokinetic study of the boron-containing prodrug of belinostat (Zl277), a pan hdac inhibitor with enhanced bioavailability. Pharmaceuticals. 2019;12(4):180.
  • (a) Feng Y, Zhang Y, Zhou D, Chen G, Li N. MicroRNAs, intestinal inflammatory and tumor. Bioorg Med Chem Lett. 2019;29(16):2051–2058. (b) Smeraldi C, Giarola A, Aggett PJ, Moldeus P, Gundert-Remy U. Use of mechanistic information to derive chemical-specific adjustment factors - refinement of risk assessment. Regul Toxicol Pharmacol. 2020;117:104776. (c) Hwu JR, Huang WC, Lin SY, Tan KT, Hu YC, Shieh FK, Bachurin SO, Ustyugov A, Tsay SC. Chikungunya virus inhibition by synthetic coumarin-guanosine conjugates. Eur J Med Chem. 2019;166:136–143.
  • Karan D, Lin MF, Johansson SL, Batra SK. Current status of the molecular genetics of human prostatic adenocarcinomas (Short Survey). Int J Cancer. 2003;103(3):285–293.
  • Cui Y, Winton MI, Zhang ZF, Rainey C, Marshall J, De Kernion JB, Eckhert CD. Dietary boron intake and prostate cancer risk. Oncol Rep. 2004;11(4):887–892.
  • Kuroda K, Liu H. The proteasome inhibitor, bortezomib, induces prostate cancer cell death by suppressing the expression of prostate-specific membrane antigen, as well as androgen receptor. Int J Oncol. 2019;54(4):1357–1366.
  • (a) Li X, Wang X, Zhang J, Hanagata N, Wang X, Weng Q, Ito A, Bando Y, Golberg D. Hollow boron nitride nanospheres as boron reservoir for prostate cancer treatment. Nat Commun. 2017;8(1):13936–13947. (b) Hacioglu C, Kar F, Kacar S, Sahinturk V, Kanbak G. High concentrations of boric acid trigger concentration-dependent oxidative stress, apoptotic pathways and morphological alterations in DU-145 human prostate cancer cell line. Biol Trace Elem Res. 2020;193(2):400–409.
  • Ozel AB, Dagsuyu E, Aydın PK, Bugan I, Bulan OK, Yanardag R, Yarat A. Brain boron level, DNA content, and myeloperoxidase activity of metformin-treated rats in diabetes and prostate cancer model. Biol Trace Elem Res. 2022;200(3):1164–1170.
  • Gallardo-Williams MT, Chapin RE, King PE, Moser GJ, Goldsworthy TL, Morrison JP, Maronpot RR. Boron supplementation inhibits the growth and local expression of IGF-1 in human prostate adenocarcinoma (LNCaP) tumors in nude mice. Toxicol Pathol. 2004;32(1):73–78.
  • McAuley EM, Bradke TA, Plopper GE. Phenylboronic acid is a more potent inhibitor than boric acid of key signaling networks involved in cancer cell migration. Cell Adh Migr. 2011;5(5):382–386.
  • Henderson KA, Kobylewski SE, Yamada KE, Eckhert CD. Boric acid induces cytoplasmic stress granule formation, eIF2α phosphorylation, and ATF4 in prostate DU-145 cells. Biometals. 2015;28(1):133–141.
  • Barranco WT, Eckhert CD. Boric acid inhibits human prostate cancer cell proliferation. Cancer Lett. 2004;216(1):21–29.
  • LeBeau AM, Singh P, Isaacs JT, Denmeade SR. Potent and selective peptidyl boronic acid inhibitors of the serine protease prostate-specific antigen. Chem Biol. 2008;15(7):665–674.
  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249.
  • Suda K, Mitsudomi T. Successes and limitations of targeted cancer therapy in lung cancer. Prog Tumor Res. 2014;41:62–77.
  • (a) Devarakonda S, Rotolo F, Tsao M-S, Lanc I, Brambilla E, Masood A, Olaussen KA, Fulton R, Sakashita S, McLeer-Florin A, et al. Tumor mutation burden as a biomarker in resected non-small-cell lung cancer. J Clin Oncol. 2018;36(30):2995–3006. (b) Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.
  • (a) Mahabir S, Spitz MR, Barrera SL, Dong YQ, Eastham C, Forman MR. Dietary boron and hormone replacement therapy as risk factors for lung cancer in women. Am J Epidemiol. 2008;167(9):1070–1080. (b) Naghii MR, Mofid M, Asgari AR, Hedayati M, Daneshpour MS. Comparative effects of daily and weekly boron supplementation on plasma steroid hormones and proinflammatory cytokines. J Trace Elem Med Biol. 2011;25(1):54–58.
  • Cebeci E, Yüksel B, Şahin F. Anti-cancer effect of boron derivatives on small-cell lung cancer. J Trace Elem Med Biol. 2022;70:126923.
  • Moot AR, Polglase A, Giles GG, Garson OM, Thursfield V, Gunter D. Men with colorectal cancer are predisposed to prostate cancer. ANZ J Surg. 2003;73(5):289–293.
  • Gillessen S, Templeton A, Marra G, Kuo YF, Valtorta E, Shahinian VB. Risk of colorectal cancer in men on long-term androgen deprivation therapy for prostate cancer. J Natl Cancer Inst. 2010;102(23):1760–1770.
  • Çiğel A, Bilgin MD, Ek RO. Evaluation of the anti-cancer and biological effects of boric acid on colon cancer cell line. Meandros. 2020;21(3):238–243.
  • Sevimli M, Bayram D, Özgöçmen M, Armağan I, Semerci Sevimli T. Boric acid suppresses cell proliferation by TNF signaling pathway mediated apoptosis in SW-480 human colon cancer line. J Trace Elem Med Biol. 2022;71:126958.
  • Eula Bingham, editor. B. C. E. Patty’s toxicology. Toxicology 2012;6(6):895–896.