Mini Review, Clin Oncol Case Rep Vol: 6 Issue: 8
Review of Boron-Based Compounds: Advancing Cancer Therapy and Beyond
Carlos A. Cardenas*
Department of Oncology, Foundation for Research and Sciences (FORESC), USA
*Corresponding Author: Adamantia Nikolaidi,
Department of OncologyFoundation for Research and Sciences (FORESC), USA.
E-mail: Karmed@live.com
Received: August 01, 2023; Manuscript No: COCR-23-110607;
Editor Assigned: August 03, 2023; PreQC Id: COCR-23-110607 (PQ);
Reviewed: August 10, 2023; QC No: COCR-23-110607 (Q);
Revised: August 14, 2023; Manuscript No: COCR-23-110607 (R);
Published: August 18, 2023; DOI: 10.4172/cocr.6(8).306
Citation: Cardenas CA (2023) Review of Boron-Based Compounds: Advancing Cancer Therapy and Beyond. Clin Oncol Case Rep 6:8
Abstract
Boron Neutron Capture Therapy (BNCT) is a pioneering medical approach seamlessly integrating the precision targeting characteristics intrinsic to chemotherapy with the anatomical localization principles underpinning conventional radiotherapy. A standout feature of BNCT is its exceptional capacity to establish a significant dosage gradient, effectively discerning between malignant tumor cells and their healthy counterparts. This defining attribute forms the basis for BNCT's clinical implementation as a robust strategy against a diverse range of malignancies.
Additionally, the discourse delves into the evolution of strategies aimed at optimizing the effectiveness of boron-based interventions. A central facet of this progression involves the vital objective of enhancing the assimilation of boron molecules into tumor cells, facilitating their targeted disintegration. To this end, an array of administration routes, including intravenous, intra-arterial, and advanced targeted nanoscale delivery systems, has been rigorously examined. This thorough exploration underscores BNCT's potential not only in minimizing undue harm to healthy tissues but also in precisely concentrating therapeutic impacts within intended tumor sites.
Moreover, beyond the ambit of BNCT, the multifaceted utility of boron-based compounds becomes evident across diverse therapeutic domains. These compounds encompass mitochondrial targeting anticancer agents and Alzheimer's disease-specific imaging probes. Additionally, they extend to encompass the inhibition of the NLRP3 inflammasome, offering new horizons for anti-inflammatory intervention. Carboranes, characterized by their distinctive pseudo-aromatic polyhedral clusters, have garnered attention as potential CNS drug development motifs, their attributes of stability, blood-brain barrier permeability, and unique structural features elevating their potential as P2X7 receptor antagonists with implications for antidepressant activity. Notably, boron-containing compounds exhibit promise in treating conditions ranging from erectile dysfunction to hormone-related diseases. These recent advances collectively underscore the remarkable versatility and potential of boron-based compounds, significantly contributing to addressing multifaceted challenges within the realm of medicinal chemistry.
Keywords: Cancer therapy, Chemotherapy, Conventional radiotherapy, Anticancer agents, Malignant tumor cells
Introduction
Boron Neutron Capture Therapy (BNCT) is an innovative medical methodology that merges the precision targeting inherent in chemotherapy with the anatomical localization principles of conventional radiotherapy. BNCT possesses a distinctive feature in its remarkable capacity to establish a substantial dosage gradient between malignant tumor cells and their healthy counterparts. This unique attribute forms the basis for the clinical adoption of BNCT as an effective strategy against malignancies, ensuring reduced impact on surrounding normal tissues while concentrating therapeutic effects specifically at the tumor site [1].
In addition, a significant focus of our discussion lies in the evolution of boron-related enhancements. A fundamental prerequisite for effective tumor cell disintegration is the incorporation of an ample quantity of boron molecules. Consequently, efforts have been dedicated to augmenting the absorption of boron compounds, leading to adaptations in administration routes and rates. Diverse approaches, encompassing intravenous, intra-arterial, and direct infusion into the internal carotid artery, have undergone exploration. Furthermore, investigations into synergistic combinations involving boron and complementary agents, such as mannitol, have been undertaken. Over time, the integration of tumor-targeting moieties and the utilization of nanoscale drug delivery systems, including liposomes and nanoparticles, have emerged as notably promising pathways. This progressive refinement of techniques and strategies underscores the dynamic nature of boron neutron capture therapy and its ongoing application within clinical contexts.
In recent years, the prevalence of Gram-negative antimicrobial resistance has become a concerning factor, particularly due to the rise in infections caused by Gram-negative bacteria in intensive care units [1]. Approximately 70% of infections in such units are attributed to Gram-negative bacteria. The increasing number of bacterial isolates showing resistance to existing antibiotics has prompted extensive efforts to develop new classes of antibiotics capable of overcoming bacterial resistance mechanisms [1]. This review explores recent advancements in boron-based compounds in medicinal chemistry and their diverse therapeutic applications.
Boron-based antibiotics: Overcoming resistance mechanisms
Efforts to combat antibiotic resistance have led to the exploration of boron-based compounds as potential antibiotics. One intriguing approach involves the inhibition of aminoacyl-tRNA synthetase and leucyl-tRNA synthetase (LeuRS) in fungi through an oxaborole tRNAtrapping (OBORT) mechanism [1]. The Plattner group introduced a series of boron-based antibiotics, with AN3365 emerging as a promising candidate. This compound exhibited potent activity against E. coli LeuRS and Gram-negative bacteria, including those carrying NDM-1, KPC carbapenemases, and P. aeruginosa. This Compound demonstrated favorable pharmacokinetics and efficacy in murine infection models against E. coli and P. aeruginosa [1].
Structural variation and SAR studies
Structural variation has proven pivotal in structure-activity relationship (SAR) studies and overall drug activity. Heteroaryls tethered at the sixth position of the benzoxaborole moiety have shown effectiveness [1]. Xia et al. synthesized novel benzoxaborole β-lactamase inhibitors, with 6-aryloxy benzoxaboroles displaying potent inhibition of AmpC P99 and CMY-2 enzymes [2]. The introduction of heteroaryl analogs to explore the effect of lipophilicity on antibacterial activity yielded promising results. Compound 68 restored the antibacterial activity of ceftazidime against Enterobacter cloacae P99-expressing AmpC, a class C β-lactamase enzyme [1].
The emergence of boranes as drug motifs
Carboranes, pseudo aromatic polyhedral clusters of boron, carbon, and hydrogen, have gained attention in medicinal chemistry. These clusters have unique structural properties, allowing for novel drug development approaches. Carboranes have been utilized for Boron Neutron Capture Therapy (BNCT), and their stability towards degradation and moisture, along with their potential to traverse the blood-brain barrier (BBB), makes them attractive for CNS drug development [1].
Carboranes as CNS-active agents
Wilkinson et al. identified closo-1,2-carborane as a novel P2X7 receptor antagonist with potential antidepressant activity. This marked the entry of carboranes as pharmacophores in CNS drug discovery. The distinctive properties of carboranes, such as metabolic stability and facile conversion to nido-carborane clusters, enable their utilization as CNS drug templates [1].
Boron compounds on therapeutics and chemoprevention strategies
In recent years, the realm of cancer therapy has witnessed a significant upsurge in the prominence of boron (B) compounds as formidable agents against aggressive and inoperable malignancies [3]. As the repertoire of B-based therapeutic chemicals expands, it becomes crucial to explore the intricate link between B and the incidence of various cancer forms, decode the underlying biochemical and molecular mechanisms influenced by B, and assess the potential of B in cancer chemoprevention.
By integrating insights from studies investigating the correlation between B-rich diets or environmental exposure to B and the regional vulnerability to specific cancer types and delving into the utilization of natural and synthetic B-containing agents as potent anticancer allies, we gain a comprehensive perspective on B's role in the cancer landscape. The focus is cast upon cancer types that particularly respond to the influence of B-containing compounds, encompassing prostate [4], breast, cervical [5], and lung cancers [6], and sarcomas [7]–[11]. The nuanced interplay of B compounds with cancer cell physiology unfolds through a myriad of mechanisms, including the inhibition of pivotal enzymatic processes, receptor binding mimicry, interference with mRNA splicing, and modulation of cell division, ultimately culminating in apoptosis induction.
What is particularly promising is the significant risk reduction observed for the prostate [4], cervical [5], colorectal [12], and lung cancers and sarcomas [9] with diets enriched in boron. This underscores the wide-ranging impact of boron on various cancer forms. As we stand at the precipice of transformative cancer therapies, boron-based compounds emerge as potent contenders for targeted cancer chemotherapy. Their distinctive advantages also warrant their inclusion in comprehensive cancer chemopreventive strategies. Through this exploration, the dynamic potential of boron compounds in reshaping the landscape of cancer management and prevention comes to the forefront, charting a path toward precision and innovation in the battle against Sarcomas [9].
Diverse therapeutic applications of boron compounds
The versatility of boron-based compounds is evident in their applications across various therapeutic areas:
Anticancer Agents: Boron-containing compounds have been designed to target mitochondria, acting as both anticancer agents and imaging probes. Additionally, boron compounds have shown the potential to improve therapeutic ratios for cancer treatment through Boron Neutron Capture Therapy (BNCT) [1].
Alzheimer's Disease Imaging: Novel boron-based fluorescent probes like CRANAD2 offer promise for Alzheimer's disease diagnosis through Aβ plaque-specific imaging [1].
Anti-Inflammatory Agents: Oxazaborines have emerged as potential inhibitors of NLRP3 inflammasome, offering a new avenue for anti-inflammatory drug development [1].
Antiandrogenic Agents: Carborane-containing compounds have demonstrated antiandrogenic activity, suggesting their potential in hormone-related disease treatments [1].
Erectile Dysfunction Treatment: Boron-containing compounds like 2(S)-amino-6-boronohexanoic acid have shown potential as arginase inhibitors for the treatment of erectile dysfunction [1].
The versatility of Boron-Based Compounds
Medicinal chemistry has witnessed remarkable progress with the development of boron-based compounds as versatile and effective agents to combat a wide spectrum of medical challenges. The escalating concern of Gram-negative antimicrobial resistance, especially in intensive care settings, necessitates novel approaches to counteract bacterial infections. Boron-based antibiotics, exemplified by AN3365 [13], have demonstrated potent activity against Gram-negative bacteria, presenting a promising solution to the escalating antimicrobial resistance crisis. Furthermore, the strategic manipulation of structural variations, such as heteroaryl substitutions, has proven instrumental in fine-tuning the antibacterial efficacy of these compounds, thus fostering new avenues for combating bacterial infections.
Carboranes, intricate pseudo aromatic polyhedral clusters, have emerged as a compelling motif in CNS drug development. Their ability to traverse the formidable Blood-Brain Barrier (BBB), stability, and distinctive structural attributes have propelled them into the spotlight of CNS-related therapeutic advancements. Recent breakthroughs, including carboranes as P2X7 receptor antagonists with potential antidepressant properties, illuminate their potential to revolutionize treatments for neurological disorders. This underscores the significance of carboranes as versatile candidates for CNS drug design, offering promising strategies for tackling neurodegenerative diseases [14].
In addition to their antimicrobial and neurological applications, boron-based compounds have exhibited promising roles in anticancer therapies, imaging techniques, and anti-inflammatory strategies.
The exploration of mitochondria-targeted agents, exemplified by FPB, showcases the ingenuity of boron chemistry in designing multifunctional compounds that not only combat cancer but also enable direct visualization of cellular processes [1]. Imaging probes like CRANAD2 have enabled the specific detection of Alzheimer's disease-related amyloid plaques, contributing to diagnostic precision in neurodegenerative conditions [15].
Recent developments in 2023 underscore the expanding potential of boron-based compounds. Ongoing research has continued to unravel novel therapeutic avenues, including treatments for allergic rhinitis, erectile dysfunction, and hormone-related diseases [16]. The FDA's approval of multiple boron-containing drugs and the steady influx of compounds into the pharmaceutical pipeline reflects th e growing interest and confidence in boron chemistry's prowess as a transformative force in modern medicine.
Conclusion
The evolution of boron's role in cancer therapy, exemplified by Boron Neutron Capture Therapy (BNCT), has ushered in a transformative era in medicinal chemistry. BNCT's seamless fusion of chemotherapy's precision with radiotherapy's localization holds immense promise for targeted and efficient ca ncer tr eatment, effectively mitigating collateral damage. Noteworthy advancements in optimizing the incorporation of boron compounds into tumors, and utilizing diverse administration routes, augur well for heightened therapeutic efficacy
Crucially, the chemotherapeutic potential of boron extends beyond BNCT. The a rena o f f ungal i nfections a nd G ram-negative bacteria combatants witnesses the prowess of boron compounds like AN3365. Structural modifications underscore their efficacy, a tra it especially pertinent in benzoxaborole moieties. The versatility of boron shines as mitochondrial-targeting agents, imaging probes for diagnostic precision, and potent anti-inflammatory tools through NLRP3 inflammasome inhibition. Further exploration reveals their potential in hormone-related conditions and erectile dysfunction.
The dynamic chemotherapeutic versatility of boron compounds like AN3365 reinforces their pivotal role in modern cancer therapy. As research progresses and applications expand, boron's transformative potential offers precision and innovation in shaping the landscape of cancer treatment outcomes.
References
- Das BC, Nandwana NK, Das S, Nandwana V, Shareef MA, et al. (2022) Boron chemicals in drug discovery and development: Synthesis and medicinal perspective. Molecules 27: 2615. [Google Scholar] [Cross Ref]
- Xia Y, Cao K, Zhou Y, Alley MRK, Rock F, et al. (2011) Synthesis and SAR of novel benzoxaboroles as a new class of β-lactamase inhibitors. Bioorg Med Chem Lett 21: 2533-2536. [Google Scholar] [Cross Ref]
- I Scorei R, Popa R (2010) Boron-containing compounds as preventive and chemotherapeutic agents for cancer. Anti-Can Agents Med Chem 10: 346-351. [Google Scholar] [Cross Ref]
- Cardenas CA (2023) The state of prostate cancer around the world - Advances in Prostate Cancer. Clin Oncol Case Rep 6: 1-4. [Google Scholar] [Cross Ref]
- Cardenas CA, Rosero AD (2023) Comprehensive insights into Human Papillomavirus (HPV) and cervical cancer: Progress, therapeutic approaches, and prospects in 2023. Clin Oncol Case Rep 6: 1-4. [Google Scholar] [Cross Ref]
- Rey S, Cardenas CA (2023) Histiocytic and granulomatous lesions of the lung. FORESC.
- Donoso PC, Perez MPS, Aguirre CC, Barbosa AO, Gomez CMG, et al. (2022) Angiosarcoma suprarrenal primario, Reporte de caso. Archivos de Patol 3: 96-103. [Google Scholar] [Cross Ref]
- Ferrer NR, Romero MB, Ochenduszko S, Perpina LG, Malagon SP, et al. (2022) Tumor fibroso solitario del tiroides. Arch Patol 3: 104-109. [Google Scholar] [Cross Ref]
- Cardenas CA (2023) Sarcomas: A comprehensive review of classification, diagnosis, treatment, and psychosocial aspects. Clin Oncol Case Rep 6: 1-4. [Google Scholar] [Cross Ref]
- Cardenas CA, Abrishami S (2023) Heartbound invaders: Reviewing rare malignant carcinomas with metastatic fervor to the Heart. Clin Oncol Case Rep 6: 1-4. [Google Scholar] [Cross Ref]
- Nodar SR, Salazar S, Cardenas C, Yllan VG (2022) Testicular tumor in children: A rare case report. Curr Prac Med Sci 9: 25-34. [Google Scholar] [Cross Ref]
- Cardenas CA, Abrishami S (2023) Colorectal carcinoma: Review and novelties in 2023. Clin Oncol Case Rep 6: 1-4. [Google Scholar] [Cross Ref]
- Biedenbach DJ, Mendes RE, Alley MRK, Sader HS, Jones R (2010) Potency and spectrum of activity of AN3365, a novel boron-containing protein synthesis inhibitor, tested against non-fermentative Gram-negative bacilli. Antimicrob Agents Chemoth 12: 15. [Google Scholar] [Cross Ref]
- Hu SQ, Hu JL, Zou FL, Liu JP, Luo HL, et al. (2022) P2X7 receptor in inflammation and pain. Brain Res Bulletin 187: 199-209. [Google Scholar] [Cross Ref]
- Leung K (2012) 5-(2E, 4E)-5-(6-hydroxy-4-oxo-2-thioxo-1, 2, 3, 4-tetrahydroxy-5 pyrimidinyl)-2, 4-pentadienylidene-2-thioxodihydro-4, 6 (1H, 5H)-pyrimidinedione. [Google Scholar] [Cross Ref]
