Preclinical antitumor activity of XK469 (NSC 656889)

LoRusso, Patricia; Parchment, Ralph E.; Demchik, Lisa; Knight, Juianna; Polin, Lisa; Dzubow, Janet; Behrens, Carl H.; Harrison, Barbara; Trainor, George L.; Corbett, Thomas H.

doi:10.1023/a:1006206814025

Cited by 45 publications

(4 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, it has been demonstrated that quinoxaline possesses antibacterial, anti‐inflammatory, antifungal, antiprotozoal, and antiviral activity (Sharma et al., 2022; Tariq et al., 2018). Figure 1 illustrates a few quinoxaline‐based drugs that cure various illnesses (Courtney et al., 2021; Cantor, 2006; Hugo & Stretton, 1964; LoRusso et al., 1998; Lin et al., 2002).…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

Nakka,

Raza,

Chaitanya

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

We designed and synthesized thirty novel quinoxaline aryl ethers as anticancer agents, and the structures of final compounds were confirmed with various analytical techniques like Mass, 1H NMR, 13C NMR, FTIR, and elemental analyses. The compounds were tested against three cancer cell lines: colon cancer (HCT‐116), breast cancer (MDA‐MB‐231), prostate cancer (DU‐145), and one normal cell line: human embryonic kidney cell line (HEK‐293). The obtained results indicate that two compounds, FQ and MQ, with IC50 values < 16 μM, were the most active compounds. Molecular docking studies revealed the binding of FQ and MQ molecules in the active site of the c‐Met kinase (PDB ID: 3F66, 1.40 Å). Furthermore, QikProp ADME prediction and the MDS analysis preserved those critical docking data of both compounds, FQ and MQ. Western blotting was used to confirm the impact of the compounds FQ and MQ on the inhibition of the c‐Met kinase receptor. The apoptosis assays were performed to investigate the mechanism of cell death for the most active compounds, FQ and MQ. The Annexin V/7‐AAD assay indicated apoptosis in MDA‐MB‐231 cells treated with FQ and MQ, with FQ (21.4%) showing a higher efficacy in killing MDA‐MB‐231 cells than MQ (14.25%). The Caspase 3/7 7‐AAD assay further supported these findings, revealing higher percentages of apoptotic cells for FQ‐treated MDA‐MB‐231 cells (41.8%). The results obtained from the apoptosis assay conclude that FQ exhibits better anticancer activity against MDA‐MB‐231 cells than MQ.

show abstract

Section: Introductionmentioning

confidence: 99%

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

Nakka,

Raza,

Chaitanya

et al. 2024

Chem Biol Drug Des

View full text Add to dashboard Cite

show abstract

“…Many of these core hybrids and their derivatives are utilized in clinics now or have entered clinical studies to treat various ailments. [28][29][30][31][32][33][34][35] These new pharmacophores' diverse pharmacological properties were explored.…”

Section: Introductionmentioning

confidence: 99%

“…In view of this, numerous attempts have been made in the literature to combine the 2‐alkoxy‐3‐cyanopyridine moiety into multiple diverse hybrids, including isatin, quinoxaline, steroids, triazolyl, glycosides, tetralin, pyrimidine, indandione, s‐triazine, coumarin and plenty of others (Figure 1). Many of these core hybrids and their derivatives are utilized in clinics now or have entered clinical studies to treat various ailments [28–35] . These new pharmacophores’ diverse pharmacological properties were explored.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Perspectives of 2‐alkoxy‐3‐Cyanopyridine Scaffolds: An Up‐to‐Date Review

Mahesha,

Shetty

2024

ChemistrySelect

View full text Add to dashboard Cite

The 2‐alkoxy‐3‐cyanopyridine derivatives’ straightforward synthesis, ease of structural manipulation, and variety of intriguing biological activity continue to captivate medicinal chemists. A substantial body of research has demonstrated that these derivatives exhibit several intriguing biological characteristics, including anticancer, antibacterial, antidiabetic, antioxidant, vasorelaxant, antiviral, and anti‐inflammatory effects. Based on the basic skeleton of 2‐alkoxy‐3‐cyanopyridine, some lead compounds have been prepared with varied pharmaceutical characteristics. These served as excellent models for the development of novel medications since they showed potential in vitro and in vivo action against several cell lines that were both drug‐susceptible and drug‐resistant. To expand the use of 2‐alkoxy‐3‐cyanopyridine in biomedicine, though, a lot more efforts are essential. To combat medication resistance and boost specificity, potential hybrids that unite the 2‐alkoxy‐3‐cyanopyridine moiety with other pharmacophores are indeed required. This review offers a summary of pharmacological screening, including studies of pertinent structure‐activity connections, action mechanisms, and potential therapeutic use.

show abstract

“…1,2 Quinoxaline derivatives are reported to have a varied range of biological properties, such as anticancer, 3 anti-malarial, anti-HIV, 4 antagonist and antibacterial properties. 5 Some of the quinoxalinecontaining derivatives that exhibit biological activities are: NCGC55879-01 (I) (Figure 1) which acts as a BRCA1 inhibitor, 6 NSC-656889, XK 469 (II) is an antineoplastic agent 7 and other quinoxaline derivatives like quinacillin (III) is a semi-synthetic penicillin with antibacterial activity 8 and AG-1296 (IV), is a protein tyrosine kinase inhibitor. 9 In addition to their medicinal importance they are also commonly used as an electron-acceptor unit, when combined with electron-donor units, these combined materials have efficient applications in photovoltaics, OLDED and dye-sensitized solar cells (DSSCs).…”

Section: Introductionmentioning

confidence: 99%

Visible light-induced metal-free synthesis of quinoxalines using Rose Bengal as a photocatalyst

Kovvuri¹,

Nagaraju²,

Kumar³

2023

Arkivoc

View full text Add to dashboard Cite

An efficient eco-friendly photocatalytic method was developed for the synthesis of pharmaceutically highly sought-after quinoxalines. This route is a simple condensation between o-phenylenediamine and an α-hydroxy ketone in methanol at room temperature in the presence of the organic dye Rose Bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) as a photocatalyst. Using this protocol, a library of examples with various ophenylenediamines and α-hydroxy ketones was prepared. This is a practically useful method for the development of quinoxaline derivatives of biological importance in good to excellent yields.

show abstract

Preclinical antitumor activity of XK469 (NSC 656889)

Cited by 45 publications

References 9 publications

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

Pharmacological Perspectives of 2‐alkoxy‐3‐Cyanopyridine Scaffolds: An Up‐to‐Date Review

Visible light-induced metal-free synthesis of quinoxalines using Rose Bengal as a photocatalyst

Contact Info

Product

Resources

About