Novel synthetic route for antimalarial benzo[a]phenoxazine derivative SSJ-183 and two active metabolites

Mizukawa, Yuki; Ge, Jian‐Feng; Bakar, Abu; Itoh, Isamu; Scheurer, Christian; Wittlin, Sergio; Brun, Reto; Matsuoka, Hiroyuki; Ihara, Masataka

doi:10.1016/j.bmc.2014.04.066

Cited by 16 publications

(15 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1) by submitting these to contemporary preclinical screening protocols and assessment of pharmacokinetic (PK) profiles. Phenoxazines have notable biological activities, and several are potently active against malaria (11,28,29). To our knowledge, however, no reports have described evaluation of the in vitro efficacies of the representative phenoxazine compounds against M. tuberculosis coupled with quantification of absorption, distribution, metabolism, and excretion (ADME) parameters and in vivo drug concentrations.…”

mentioning

confidence: 99%

In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

Tanner

Evans

Seldon

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Mycobacterium tuberculosis, the causative agent of tuberculosis, remains a leading infectious killer globally, demanding the urgent development of faster-acting drugs with novel mechanisms of action. Riminophenazines such as clofazimine are clinically efficacious against both drug-susceptible and drug-resistant strains of M. tuberculosis. We determined the in vitro anti-M. tuberculosis activities, absorption, distribution, metabolism, and excretion properties, and in vivo mouse pharmacokinetics of a series of structurally related phenoxazines. One of these, PhX1, displayed promising drug-like properties and potent in vitro efficacy, supporting its further investigation in an M. tuberculosis-infected animal model.

show abstract

mentioning

confidence: 99%

In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

Tanner

Evans

Seldon

et al. 2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…In another report, one-pot synthesis of benzo[a]phenoxazine derivative SJ-183 lead 14 a and its N-de-ethylated 14 b and bis-N,N-deethylated 14 c metabolites were described. [29] Their antimalarial activities showed comparable and approximately two-fold increased IC 50 against drug-sensitive and drugresistant Plasmodium falciparum parasites ( Table 2). Previously, higher activities against P. falciparum were recorded in the in-vitro screening of benzo[a]phenoxazine class of SJ-183 compounds possessing hetero-aromatic rings on position-6 and compound 14 a, in particular, showed the rapid onset of action comparable to artesunate antimalarial drug.…”

Section: Phenoxazines As Antimalarial Agentsmentioning

confidence: 98%

Recent Development in Applications of Synthetic Phenoxazines and Their Related Congeners: A Mini‐Review

2020

View full text Add to dashboard Cite

Phenoxazines have gained enormous interest because of their diverse applications in both material science and chemotherapy. They exhibit numerous biological activities, ranging from anti‐malarial, anticancer, antiviral, antidiabetic, anti‐Alzheimer, antioxidant, anti‐inflammatory, to antibiotic and many more. Actinomycin D, for instance, which embodies a phenoxazine scaffold, displays both antibiotic and anticancer property. Phenoxaxines have also found usefulness in organic light‐emitting diodes, fluorescent probes and dye‐sensitized solar cells. Over the years, various research groups have strived for several structural modifications targeting new derivatives of phenoxazines with improved properties. This present review highlights the progress, challenges and prospects in medicinal and material applications of phenoxazine moiety to provide greater insight into the development of future derivatives with improved properties.

show abstract

“…During our continuing project for developing new generation of PSs [ 7 , 8 , 9 , 10 ], the benzo[ a ]phenoxazinium chlorides dyes came to our attention due to their good photostability, high molar absorption, long-wavelength absorption, and relative low fluorescence quantum yield [ 11 , 12 , 13 ]. Literature survey indicated that benzo[ a ]phenoxazinium derivatives exhibited antifungal [ 12 , 14 ], and antimalarial activity [ 15 ], and especially functioned as PSs in antimicrobial PDT [ 15 , 16 , 17 , 18 ]. However, to our knowledge, the potential anticancer PDT of benzo[ a ]phenoxazinium dyes has been little investigated [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

et al. 2018

View full text Add to dashboard Cite

The use of photodynamic therapy (PDT) and development of novel photosensitizers (PSs) for cancer treatment have received more and more attention nowadays. In the present work, five benzo[a]phenoxazinium derivatives have been prepared and evaluated for their in vitro anticancer photodynamic activity for the first time. They are red light absorbers and show low fluorescence quantum yield. Of these compounds, PS4 exhibited a higher quantum yield for reactive oxygen species (ROS) generation. The assays with cells in vitro showed that PS1 and PS4 were not significantly toxic in the dark, but was robustly toxic against the murine breast adenocarcinoma cells 4T1 and normal murine fibroblast cells NIH-3T3 upon photoactivation. More interestingly, PS5 was particularly selective towards 4T1 cancer cells and nearly non-phototoxic to non-cancerous NIH-3T3 cells. The results described in this report suggest that these new benzo[a]phenoxazinium derivatives are potential candidates as PSs for anticancer PDT. Further investigation of benzo[a]phenoxaziniums for anticancer PDT is warranted.

show abstract

Novel synthetic route for antimalarial benzo[a]phenoxazine derivative SSJ-183 and two active metabolites

Cited by 16 publications

References 7 publications

In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

In Vitro Efficacies, ADME, and Pharmacokinetic Properties of Phenoxazine Derivatives Active against Mycobacterium tuberculosis

Recent Development in Applications of Synthetic Phenoxazines and Their Related Congeners: A Mini‐Review

Synthesis and Evaluation of New Potential Benzo[a]phenoxazinium Photosensitizers for Anticancer Photodynamic Therapy

Contact Info

Product

Resources

About