117098-94-9Relevant articles and documents
Synthesis and biological evaluation of arylphosphonium-benzoxaborole conjugates as novel anticancer agents
Jonnalagadda, Shirisha,Jonnalagadda, Sravan K.,Jonnalagadda, Subash C.,Kiprof, Paul,Mereddy, Venkatram R.,Ronayne, Conor T.,Wielenberg, Kevin
, (2020)
Arylphosphonium-benzoxaborole conjugates have been synthesized as potential mitochondria targeting anticancer agents. The synthesized compounds have been tested for their effects on cell viability in various solid tumor cell lines including breast cancer 4T1 and MCF-7, pancreatic cancer MIAPaCa-2 and colorectal adenocarcinoma WiDr. Compound 6c is designated as a lead compound for further studies due to its enhanced effects on cell viability in the above-mentioned cell lines. Seahorse Xfe96 based metabolic assays reveal that the lead candidate 6c inhibits mitochondrial respiration in 4T1 and WiDr cell lines as evidenced by the reduction of mitochondrial ATP production and increase in proton leak. Epiflourescent microscopy experiments also illustrate that 6c causes significant mitochondrial fragmentation in 4T1 and WiDr cells, morphologically consistent with programmed cell death. Our current studies illustrate that arylphosphonium-benzoxaborole conjugates have potential to be further developed as anticancer agents.
Synthesis and evaluation of functionalized aminobenzoboroxoles as potential anti-cancer agents
Suman, Pathi,Patel, Bhawankumar P.,Kasibotla, Agasthya V.,Solano, Lucas N.,Jonnalagadda, Subash C.
, p. 125 - 131 (2015)
Several aminobenzoboroxole derivatives have been prepared starting from o-boronobenzaldehyde employing reductive amination protocol. The corresponding aminobenzoboroxole derivatives have been further functionalized as N-nitrosoaminobenzoboroxoles as well as N-benzoboroxolylureas. These derivatives have been evaluated for their anti-cancer activity on human pancreatic cancer MIAPaCa-2 and human breast cancer MDA-MB-231 cell lines. 2015 Elsevier Ltd. All rights reserved.
Benzoxaboroles as dynamic covalent receptors for bioconjugation and transport of nucleosides and related drugs: Proof of action in HeLa cells
Samaniego Lopez, Cecilia,Martínez, Jimena H.,Acebedo, Sofía L.,Spagnuolo, Carla C.
, (2019)
In this work we describe not previously explored binding studies on the reversible interaction of benzoxaborole with ligands of medical and pharmaceutical interest such as nucleosidic drugs gemcitabine and capecitabine, as well as the hydrophobic chemotherapeutic doxorubicin. We include functional derivatives of benzoxaborole such as a near infrared fluorescent boronolectine, Cy-Bx, The dynamic covalent interaction in physiological conditions was assessed by spectroscopic techniques yielding moderate to high binding affinities. The cytotoxic activity of the drugs upon conjugation to the boronolectins was evaluated revealing significant influence of the bioconjugation status on the cellular viability. The availability of the conjugate for cellular uptake and localization in the model cancer cell line HeLa was assessed by fluorescence imaging. Benzoxaborole and the fluorescent boronolectin Cy-Bx, proved to be versatile conjugation tools for 1,2 and 1,3-diol containing pharmacophores as well as bioisosteric forms such as 1,2-hydroxyamino, envisioning these small boronolectins as components in systems for drug release with tracking capability.
Inhibiting protein prenylation with benzoxaboroles to target fungal plant pathogens
Cowen, Leah E.,Frederick, Brittany H.,Kim, Sang Hu,Liu, C. Tony,Liu, Chunliang,Mcgregor, Cari,Steere, Luke,Whitesell, Luke,Zhang, Yong-Kang,Zhou, Yasheen
, p. 1930 - 1941 (2020/07/14)
Fungal pathogens pose an increasing threat to global food security through devastating effects on staple crops and contamination of food supplies with carcinogenic toxins. Widespread deployment of agricultural fungicides has increased crop yields but is driving increasingly frequent resistance to available agents and creating environmental reservoirs of drug-resistant fungi that can also infect susceptible human populations. To uncover non-cross-resistant modes of antifungal action, we leveraged the unique chemical properties of boron chemistry to synthesize novel 6-thiocarbamate benzoxaboroles with broad spectrum activity against diverse fungal plant pathogens. Through whole genome sequencing of Saccharomyces cerevisiae isolates selected for stable resistance to these compounds, we identified mutations in the protein prenylation-related genes, CDC43 and ERG20. Allele-swapping experiments confirmed that point mutations in CDC43, which encodes an essential catalytic subunit within geranylgeranyl transferase I (GGTase I) complex, were sufficient to confer resistance to the benzoxaboroles. Mutations in ERG20, which encodes an upstream farnesyl pyrophosphate synthase in the geranylgeranylation pathway, also conferred resistance. Consistent with impairment of protein prenylation, the compounds disrupted membrane localization of the classical geranylgeranylation substrate Cdc42. Guided by molecular docking predictions, which favored Cdc43 as the most likely direct target, we overexpressed and purified functional GGTase I complex to demonstrate direct binding of benzoxaboroles to it and concentration-dependent inhibition of its transferase activity. Further development of the boron-containing scaffold described here offers a promising path to the development of GGTase I inhibitors as a mechanistically distinct broad spectrum fungicide class with reduced potential for cross-resistance to antifungals in current use.
