Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

Macdonald, Cynthia; Lyzenga, Wendy J.; Шао, Ди; Agu, Remigius U.

doi:10.3109/10717541003777548

Cited by 10 publications

(6 citation statements)

References 17 publications

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“…toxicity may not be the direct result of the organometallic complexes. Similar concentra-tions of DMSO have been shown to be cytotoxic to both cell lines in other reports [41,42]. There were no significant differences between 50 µg/mL and DMSO controls for either complex in both cell lines.…”

Section: Toxicity Testing Of Complexes 2 Andsupporting

confidence: 80%

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

Chuong

DuChane

Webb

et al. 2021

Viruses

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SARS-CoV-2 emerged in 2019 as a devastating viral pathogen with no available preventative or treatment to control what led to the current global pandemic. The continued spread of the virus and increasing death toll necessitate the development of effective antiviral treatments to combat this virus. To this end, we evaluated a new class of organometallic complexes as potential antivirals. Our findings demonstrate that two pentamethylcyclopentadienyl (Cp*) rhodium piano stool complexes, Cp*Rh(1,3-dicyclohexylimidazol-2-ylidene)Cl2 (complex 2) and Cp*Rh(dipivaloylmethanato)Cl (complex 4), have direct virucidal activity against SARS-CoV-2. Subsequent in vitro testing suggests that complex 4 is the more stable and effective complex and demonstrates that both 2 and 4 have low toxicity in Vero E6 and Calu-3 cells. The results presented here highlight the potential application of organometallic complexes as antivirals and support further investigation into their activity.

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Section: Toxicity Testing Of Complexes 2 Andsupporting

confidence: 80%

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

Chuong

DuChane

Webb

et al. 2021

Viruses

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“…Starting from day 15 of drug therapy and until the end of the experimental period, RM-133-treated tumors became significantly smaller than in the control group, with a 60% difference between the two groups measured at the end of the treatment. Since the toxic potential of a given compound depends on its concentration and exposure time [ 37 ], and as mortality, clinical symptoms, and body weight changes are among the main indicators of its toxicity [ 38 ], it is noteworthy that over a 21-day treatment period with RM-133, there was no apparent effect on body weight ( Fig 3B ) nor apparent toxicity of the drug (e.g. abnormal behavior, death).…”

Section: Resultsmentioning

confidence: 99%

The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers

et al. 2015

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Ovarian and pancreatic cancers are two of the most aggressive and lethal cancers, whose management faces only limited therapeutic options. Typically, these tumors spread insidiously accompanied first with atypical symptoms, and usually shift to a drug resistance phenotype with the current pharmaceutical armamentarium. Thus, the development of new drugs acting via a different mechanism of action represents a clear priority. Herein, we are reporting for the first time that the aminosteroid derivative RM-133, developed in our laboratory, displays promising activity on two models of aggressive cancers, namely ovarian (OVCAR-3) and pancreatic (PANC-1) cancers. The IC50 value of RM-133 was 0.8 μM and 0.3 μM for OVCAR-3 and PANC-1 cell lines in culture, respectively. Based on pharmacokinetic studies on RM-133 using 11 different vehicles, we selected two main vehicles: aqueous 0.4% methylcellulose:ethanol (92:8) and sunflower oil:ethanol (92:8) for in vivo studies. Using subcutaneous injection of RM-133 with the methylcellulose-based vehicle, growth of PANC-1 tumors xenografted to nude mice was inhibited by 63%. Quite interestingly, RM-133 injected subcutaneously with the methylcellulose-based or sunflower-based vehicles reduced OVCAR-3 xenograft growth by 122% and 100%, respectively. After the end of RM-133 treatment using the methylcellulose-based vehicle, OVCAR-3 tumor growth inhibition was maintained for ≥ 1 week. RM-133 was also well tolerated in the whole animal, no apparent sign of toxicity having been detected in the xenograft studies.

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“…Therefore, it is advised to consider DMSO as a first-choice solvent and NMP as an alternative if, for some reason, it is not applicable. Notably, DMSO is often used as a solubilizing agent in biological activity measurements, including enzyme inhibition and in vitro assays using cell cultures [ 56 , 57 , 58 ]. The aqueous solubility of the majority of pharmaceuticals is very low, which would make it difficult to carry out this type of measurement in pure aqueous solutions.…”

Section: Resultsmentioning

confidence: 99%

Finding the Right Solvent: A Novel Screening Protocol for Identifying Environmentally Friendly and Cost-Effective Options for Benzenesulfonamide

2023

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This study investigated the solubility of benzenesulfonamide (BSA) as a model compound using experimental and computational methods. New experimental solubility data were collected in the solvents DMSO, DMF, 4FM, and their binary mixtures with water. The predictive model was constructed based on the best-performing regression models trained on available experimental data, and their hyperparameters were optimized using a newly developed Python code. To evaluate the models, a novel scoring function was formulated, considering not only the accuracy but also the bias–variance tradeoff through a learning curve analysis. An ensemble approach was adopted by selecting the top-performing regression models for test and validation subsets. The obtained model accurately back-calculated the experimental data and was used to predict the solubility of BSA in 2067 potential solvents. The analysis of the entire solvent space focused on the identification of solvents with high solubility, a low environmental impact, and affordability, leading to a refined list of potential candidates that meet all three requirements. The proposed procedure has general applicability and can significantly improve the quality and speed of experimental solvent screening.

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Water-soluble organic solubilizers for in vitro drug delivery studies with respiratory epithelial cells: Selection based on various toxicity indicators

Cited by 10 publications

References 17 publications

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

Noble Metal Organometallic Complexes Display Antiviral Activity against SARS-CoV-2

The Aminosteroid Derivative RM-133 Shows In Vitro and In Vivo Antitumor Activity in Human Ovarian and Pancreatic Cancers

Finding the Right Solvent: A Novel Screening Protocol for Identifying Environmentally Friendly and Cost-Effective Options for Benzenesulfonamide

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