New Norcantharidin Analogs: Synthesis and Anticancer Activity

Pachuta‐Stec, Anna; Szuster‐Ciesielska, Agnieszka

doi:10.1002/ardp.201500255

Cited by 10 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The MTT colorimetric assay (Mosmann, ) was conducted as described elsewhere (Pachuta‐Stec & Szuster‐Ciesielska, ). Briefly, an MTT solution (25 μl of 5 mg/ml in PBS; Sigma‐Aldrich) was added to each well containing cultured cells.…”

Section: Methodsmentioning

confidence: 99%

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Szuster‐Ciesielska

Urban‐Chmiel

Wernicki

et al. 2018

Vet Pharm & Therapeutics

Self Cite

View full text Add to dashboard Cite

Escherichia coli is one of the major pathogens in humans and animals causing localized and systemic infections, which often lead to acute inflammation, watery diarrhea, and hemorrhagic colitis. Bacterial lipopolysaccharide (LPS) and Shiga exotoxins (Stx) are mostly responsible for such clinical signs. Therefore, highly effective treatment of E. coli infections should include both eradication of bacteria and neutralization of their toxins. Here, for the first time, we compared the in vitro ability of common antibiotics to decrease LPS- and Stx-mediated cytotoxicity: colistin, amoxicillin (used separately or combined), enrofloxacin, and its metabolite ciprofloxacin. Three experimental scenarios were realized as follows: (a) the direct effect of antibiotics on endotoxin, (b) the effect of antibiotic treatment on LPS-mediated cytotoxicity in an experiment mimicking "natural infection," (c) the effect of antibiotics to decrease Stx2e-mediated cytotoxicity. Two cell lines, A549 and Vero cells, were used to perform cytotoxic assays with the methyl tetrazolium (MTT) and lactate dehydrogenase leakage (LDH) methods, respectively. Colistin and amoxicillin, especially used in combination, were able to attenuate LPS toxic effect, which was reflected by increase in A549 cell viability. In comparison with other antibiotics, the combination of colistin and amoxicillin exhibited the highest boster or additive effect in protecting cells against LPS- and Stx2e-induced toxicity. In summary, in comparison with fluoroquinolones, the combination of colistin and amoxicillin at concentrations similar to those achieved in plasma of treated animals exhibited the highest ability to attenuate LPS- and Stx2e-mediated cytotoxicity.

show abstract

Section: Methodsmentioning

confidence: 99%

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Szuster‐Ciesielska

Urban‐Chmiel

Wernicki

et al. 2018

Vet Pharm & Therapeutics

Self Cite

View full text Add to dashboard Cite

show abstract

“…In light of these reported effects, norcantharidin has been subjected to multiple SAR studies. As outlined in Figure , previously reported analogues include cantharimides 3 , acid amides 4 ,– bis‐norcantharidimides 5 , anhydride‐modified analogues 6 , and a series including terminal phosphate esters exemplified by 7 . Furthermore, a number of norcantharidin‐tethered analogues have been reported, the most recent of which include a series of podophyllotoxin–norcanthardin hybrids exemplified by 8 .…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of a Series of Norcantharidin‐Inspired Tetrahydroepoxyisoindole Carboxamides

et al. 2017

View full text Add to dashboard Cite

A series of 28 norcantharidin (NorC)-inspired analogues were accessed via a robust two-step Ugi intramolecular Diels-Alder (IMDA) sequence. Four analogues displayed whole-cell cytotoxicity equipotent to that of NorC and cisplatin against a number of cancer cell lines and a normal breast cell line (MCF10A). Notably, (3S,3aS,6R)-2-benzyl-7-methyl-N-(naphthalen-2-yl)-1-oxo-1,2,3,6-tetrahydro-3a,6-epoxyisoindole-3-carboxamide (trans-27) displayed superior whole-cell activity against breast (MCF-7, GI =2.9 μm) and colon (HT29, GI =6.4 μm) cancer cell lines relative to the control (cisplatin), which elicited respective GI values of 6.5 and 11.3 μm against the aforementioned cell lines. This analogue also displayed improved activity relative to NorC across the breast (MCF-7, GI =2.9 μm; NorC GI =7.5 μm), ovarian (A2780, GI =2.2 μm; NorC GI =4.4 μm), and neuroblastoma (BE2-C, GI =2.2 μm; NorC GI =3.7 μm) cancer cell lines. Structure-activity relationship (SAR) investigations demonstrated that retention of sp hybridized connections within the tetrahydroepoxyisoindole carboxamide scaffold is crucial, as aromatization to a phenolic functionality decreased activity, whereas removal of a single olefin bond abolished cytotoxicity. Nonetheless, with respect to the latter, use of crotonic acid as opposed 2-butynoic acid in the Ugi-IMDA sequence imparted a significant improvement to diastereoselectivity, with the cis/trans isomer ratio shifting from ≈1:1.2 to ≈0.5:9.5.

show abstract

“…NCTD's action mechanism Pharmaceuticals 2023, 16, 501 2 of 18 includes the inhibition of protein phosphatases PP1 and PP2, which play a vital role in cell cycle regulation [6]. Moreover, the anhydride moiety in NCTD has been suggested as an effective alternative to treat several types of cancer, including neuroblastoma, glioblastoma, and melanoma [7]. Despite the shown promise, NCTD's use is limited due to its low aqueous solubility (maximum of 2.5 mg/mL at pH 6, and 9.5 mg/mL at pH 9.5), which hinders the obtainment of a high drug strength in formulations for potential administration [8].…”

Section: Introductionmentioning

confidence: 99%

Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells

et al. 2023

View full text Add to dashboard Cite

Melanoma is a highly lethal type of cancer that has had an increase in incidence in the last decades. Nevertheless, current therapies lack effectiveness and have highly disabling side effects, which calls for new therapeutic strategies. Norcantharidin (NCTD) is an acid derivative with potential antitumor activity isolated from natural blister beetles. However, its solubility limitations restrict its use. To address this issue, we developed an oil-in-water nanoemulsion using commonly available cosmetic ingredients, which increased NCTD solubility 10-fold compared to water. The developed nanoemulsion showed a good droplet size and homogeneity, with adequate pH and viscosity for skin application. In vitro drug release studies showed a sustained release profile, ideal for prolonged therapeutic effects. Accelerated stability studies proved that the formulation was reasonably stable under stress conditions, with particle separation fingerprints, instability index, particle size, and sedimentation velocity analyses being conducted. To assess the therapeutic potential of the developed formulation, in vitro studies were conducted on melanoma B16F1 cells; results showed an IC50 of 1.026 +/− 0.370 mg/kg, and the cells’ metabolic activity decreased after exposure to the NCTD nanoemulsion. Hence, a new “easy-to-make” nanoformulation with therapeutic potential on melanoma cells was developed, as a possible adjuvant for future melanoma treatment.

show abstract

New Norcantharidin Analogs: Synthesis and Anticancer Activity

Cited by 10 publications

References 48 publications

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Cytotoxicity of a Series of Norcantharidin‐Inspired Tetrahydroepoxyisoindole Carboxamides

Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells

Contact Info

Product

Resources

About

New Norcantharidin Analogs: Synthesis and Anticancer Activity

Cited by 10 publications

References 48 publications

Evaluation of the ability of colistin, amoxicillin (components of Potencil®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Evaluation of the ability of colistin, amoxicillin (components of Potencil®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Cytotoxicity of a Series of Norcantharidin‐Inspired Tetrahydroepoxyisoindole Carboxamides

Norcantharidin Nanoemulsion Development, Characterization, and In Vitro Antiproliferation Effect on B16F1 Melanoma Cells

Contact Info

Product

Resources

About

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies

Evaluation of the ability of colistin, amoxicillin (components of Potencil^®), and fluoroquinolones to attenuate bacterial endotoxin‐ and Shiga exotoxin‐mediated cytotoxicity—In vitro studies