In vitro anticancer activity and SAR studies of triazolyl aminoacyl(peptidyl) penicillins

Cornier, Patricia G.; Delpiccolo, Carina M. L.; Mascali, Florencia C.; Boggián, Dora B.; Mata, Ernesto G.; Cárdenas, Mariano; Blank, Viviana C.; Roguin, Leonor P.

doi:10.1039/c3md00332a

Cited by 16 publications

(14 citation statements)

References 31 publications

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“…TAP7f was synthesized as described in a previous work (Figure 1, Cornier et al, 2014). A 100 mM stock solution of the compound was prepared in dimethyl sulfoxide (DMSO) and stored at −70°C.…”

Section: Reagents and Antibodiesmentioning

confidence: 99%

“…We have previously reported that TAP7f induces an antiproliferative activity on different tumor cell lines (Cornier et al, 2014;Blank et al, 2018). In this work, we explored TAP7f effect on the proliferation of metastatic cells from different sources ( Table 1).…”

Section: Tap7f Inhibits Proliferation Of Different Metastatic Cellsmentioning

confidence: 99%

“…Therefore, the finding of new compounds that can inhibit melanoma metastasis is crucial and a main challenge to be solved. In a previous work, we have obtained and characterized a series of penicillin derivatives (triazolylaminoacyl(peptidyl) penicillins: TAPs) that were obtained by conjugation of penicillin to different aminoacids or dipeptides via a triazole group (Cornier et al, 2014). The triazolylpeptidyl penicillin derivative TAP7f, with leucine and phenylalanine bound to the triazole group, was the most potent and selective TAP tested, showing 30 times more antiproliferative activity on tumor cells than on normal cells (Cornier et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

“…In a previous work, we have obtained and characterized a series of penicillin derivatives (triazolylaminoacyl(peptidyl) penicillins: TAPs) that were obtained by conjugation of penicillin to different aminoacids or dipeptides via a triazole group (Cornier et al, 2014). The triazolylpeptidyl penicillin derivative TAP7f, with leucine and phenylalanine bound to the triazole group, was the most potent and selective TAP tested, showing 30 times more antiproliferative activity on tumor cells than on normal cells (Cornier et al, 2014). We have also demonstrated that TAP7f induced an antitumor effect through the induction of cell cycle arrest and the activation of both death receptor and mitochondria-dependent apoptotic pathways in melanoma B16-F0 cells (Blank et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway

et al. 2020

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The synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin avb3 expression and Wnt/b-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrixmetalloproteinases-2 and-9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcription factor Snail and the mesenchymal markers vimentin, and N-cadherin, and up-regulated the expression of the epithelial marker E-cadherin, suggesting that the penicillin derivative affects epithelial-mesenchymal transition. Results obtained in vitro were supported by those obtained in a B16-F10-bearing mice metastatic model, that showed a significant TAP7f inhibition of lung metastasis. These findings suggest the potential of TAP7f as a chemotherapeutic agent for the treatment of metastatic melanoma.

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Section: Reagents and Antibodiesmentioning

confidence: 99%

Section: Tap7f Inhibits Proliferation Of Different Metastatic Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway

et al. 2020

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“…Penisilinlerin serviks ve lösemik kanser hücreleri üzerine etkisini düşük dozlarda bile gösteren çalışmalar yayınlanmıştır [7] . Yine son dönemde peptidil-penisilinlerin in vitro ortamda hızlı çoğalan hücreler üzerine etkileri gösterilmiş ve bu konuda gelecekte ümit vaat edici oldukları bildirilmiştir [8] . Penisilinlerin anti-kanser etkileri üzerine çalışmalar devam edecek gibi görünmektedir.…”

Section: Anti-kanser Etkiunclassified

Non Antimicrobial Effects of Antibacterial Agents

Demiraslan¹,

Uysal²

2018

mjima

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Aside from their antibacterial activity, antimicrobial agents have also some beneficial effects due to their chemical structures. These effects include anti-inflammatory, immunomodulatory, anti-cancer, anti-angiogenic, neuroprotective, cardioprotective, augmented gastrointestinal motility, and binding toxins. This paper does not comprise non-antimicrobial effects of all antibiotics due to the fact that the issue is very extended. We reviewed use of penicillins in mushroom poisoning and their promising inhibitor effect on proliferation of cervical carcinoma and leukemia cells. We summarized neuroprotective effect of ceftriaxone and its inhibitory potential on proliferation of lung cancer cells. Tetracyclines are agents that have been focused on and investigated for a long time, and demeclocycline that belongs to this group is used for inappropriate antidiuretic hormone secretion. Moreover, low-dose doxycycline that is also a tetracycline, has been approved for the treatment of periodontitis, and inhibition of matrix metalloproteinase enzyme is the responsible mechanism for its anti-inflammatory action. Matrix metalloproteinase inhibition also provides a decrease in tumor angiogenesis and metastasis. Minocycline, another tetracycline, reduces the synthesis of beta-amyloid which plays a key role in Alzheimer's disease and other neurodegenerative diseases, and it also inhibits glial inducible nitric oxide (NO) synthase and NOmediated neurotoxicity. Erythromycin that is a macrolide antibiotic is used as a gastrointestinal motility augmenter; azithromycin gives an early improvement in patients with cystic fibrosis due to its anti-inflammatory effect. It has been shown that clarithromycin decreases the metastatic AbstractAntimikrobiyal ajanlar kimyasal yapılarından dolayı bakterilere karşı aktiviteleri dışında bazı yararlı etkilere de sahiptirler. Bunlar arasında antienflamatuvar, immünomodülatör, anti-kanser, anti-anjiyogenik, nöroprotektif, kardiyoprotektif, gastrointestinal hareket artırıcı ve toksin bağlayıcı etkiler sayılabilir. Bu yazıda, konu çok geniş olduğundan dolayı sınırlı sayıda antibiyotiğin antimikrobiyal dışı etkileri ele alınmıştır. Penisilinlerin serviks ve lösemik kanser hücrelerinin çoğalmasını durdurma konusunda ümit vaat edici etkisi ve mantar zehirlenmesi tedavisinde kullanımı; seftriaksonun akciğer kanseri hücreleri üzerindeki çoğalmayı önleyici potansiyeli ve nöroprotektif etkisi derlenmiştir. Tetrasiklinler uzun süredir üzerinde durulan ve araştırılan ajanlardır ve bu gruptaki demeklosiklin, uygunsuz antidiüretik hormon salınımında kullanılmaktadır. Ayrıca tetrasiklinlerden doksisiklin düşük dozda periodontit tedavisi için onay almıştır ve anti-enflamatuvar etkiden sorumlu mekanizma matriks metalloproteinaz (MMP) enzimi inhibisyonudur. Ayrıca MMP inhibisyonu metastazda ve tümör anjiyogenezinde azaltma da sağlayabilmektedir. Diğer bir tetrasiklin olan minosiklin ise Alzheimer ve diğer nörodejeneratif hastalıklarda kilit rolü olan beta-amilod sentezini azaltmakta ve ayrıca gliyal indüklenebilir ...

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