In Vitro Anticancer and Antivirus Activities of Cyano- And Bis (Trifluoromethylsulfonyl) imide-Based Ionic Liquids

In the current work, we present a broad analysis of cytotoxicity toward normal (kidney and lung) and cancer (lung, liver, and cervix) cells of ionic liquids (ILs) with imidazolium cations and cyano-based or bis(trifluoromethylsulfonyl)imide anions. Additionally, we verify if ILs might be candidates for new potential virucidal agents. We observed the highest biological activity for 1-methyl-3- octylimidazolium bis(trifluoromethylsulfonyl)imide, whereas the least toxic was 1-ethyl-3-methylimidazolium thiocyanate. We found that all investigated ILs revealed a lack of antiviral activity against viruses: human parainfluenza virus type 3 (HPIV-3), human adenovirus 5 (AdV5), human herpesvirus 1 (HSV-1), and human herpesvirus 5 (HCMV) in nontoxic concentrations

Ruthenium Dendrimers against Human Lymphoblastic Leukemia 1301 Cells

Ruthenium atoms located in the surfaces of carbosilane dendrimers markedly increase their anti-tumor properties. Carbosilane dendrimers have been widely studied as carriers of drugs and genes owing to such characteristic features as monodispersity, stability, and multivalence. The presence of ruthenium in the dendrimer structure enhances their successful use in anti-cancer therapy. In this paper, the activity of dendrimers of generation 1 and 2 against 1301 cells was evaluated using Transmission Electron Microscopy, comet assay and Real Time PCR techniques. Additionally, the level of reactive oxygen species (ROS) and changes of mitochondrial potential values were assessed. The results of the present study show that ruthenium dendrimers significantly decrease the viability of leukemia cells (1301) but show low toxicity to non-cancer cells (peripheral blood mononuclear cells—PBMCs). The in vitro test results indicate that the dendrimers injure the 1301 leukemia cells via the apoptosis pathway.Funding: This work was co-financed by the Project EUROPARTNER of Polish National Agency for Academic Exchange (NAWA) and Pl-SK 2019–2020 bilateral project -PPN/BIL/2018/1/00150; supported by the project “NanoTENDO” granted by National Science Centre, Poland under the M-ERA.NET 2 of Horizon 2020 programme, project No: 685451. This research was also supported by grants from CTQ2017-86224-P (MINECO), consortiums IMMUNOTHERCAN-CM B2017/BMD-3733, NANODENDMED II-CM ref B2017/BMD-3703 and Project SBPLY/17/180501/000358 Junta de Comunidades de Castilla-La Mancha (JCCM). CIBER-BBN is an initiative funded by the VI National R&D&I Plan 2008–2011, IniciativaIngenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. Acknowledgments: N.S.d.O. wishes to thank JCCM for a predoctoral fellowship. This article is based upon work from COST Action CA17140 “Cancer Nanomedicine from the Bench to the Bedside” supported by COST(European Cooperation in Science and Technology)

The effect of doxorubicin derivatives with modified daunosamine on ovarian cancer cells

Niewątpliwym ograniczeniem w stosowaniu doksorubicyny jest wysoka kardiotoksyczność oraz zjawisko oporności wielolekowej (MDR). Obecność wolnej grupy –NH2 daunozaminy uważana była przez wiele lat jako kluczowy element dla aktywności przeciwnowotworowej antracyklin. Liczne badania naukowe dowodzą, że korzystne rezultaty dają modyfikacje grupy aminowej daunozaminy w pozycji C-3’. Wśród badanych w ramach pracy doktorskiej analogów znalazły się takie, w których dokonano zamiany grupy –NH2 znajdującej się przy atomie węgla C-3’ daunozaminy na trójpodstawioną grupę amidynową zawierającą reszty cyklicznych amin drugorzędowych (–NRR) takich jak piperydyna (DOX-F PIP), pirolidyna (DOX-F PYR), morfolina (DOX-F MOR), heksametylenoimina (DOX-F HEX) iN-metylopiperazyna (DOX-F PAZ) oraz pierścień oksazolinowy (O-DOX). Badane analogi wykazują lepsze właściwości cytotoksyczne w porównaniu z macierzystą doksorubicyną w komórkach raka jajnika opornych na związek referencyjny. Wykazano ponadto zwiększoną zdolność do indukcji apoptozy i wysoką genotoksyczność. Co ważne, dostępne dane literaturowe dowodzą także, że zmodyfikowane związki wykazują niższą niż związek referencyjny toksyczność ogólnoustrojową, w szczególności kardiotoksyczność. Ponadto, badane pochodne doksorubicyny posiadają zdolność do przełamywania oporności wielolekowej in vitro, w przeciwieństwie do leków macierzystych. Biorąc pod uwagę wyniki przeprowadzonych badań można stwierdzić, że zastosowana modyfikacja chemiczna w pozycji C-3’ jest skuteczną metodą dla otrzymania związków o wyższej niż doksorubicyna aktywności biologicznej.Indywidualne stypendia stanowiące dofinansowanie badań mieszczących się w temacie Wpływ wybranych pochodnych doksorubicyny na komórki raka jajnika (Rozporządzenie MNiSW z 5 listopada 2010 r.

Cytotoxic effects of halophilic archaea metabolites on ovarian cancer cell lines

Abstract Background Ovarian cancer is one of the most frequent and deadly gynaecological cancers, often resistant to platinum-based chemotherapy, the current standard of care. Halophilic microorganisms have been shown to produce a large variety of metabolites, some of which show toxicity to various cancer cell lines. However, none have yet been shown to be active against ovarian cancer cells. Here, we examined the effects of metabolites secreted by the halophilic archaea Halorhabdus rudnickae and Natrinema salaciae on various cancer cell lines, including ovarian cancer cell lines. Results 1H NMR analyses of Hrd. rudnickae and Nnm. salaciae culture supernatants contain a complex mixture of metabolites that differ between species, and even between two different strains of the same species, such as Hrd. rudnickae strains 64T and 66. By using the MTT and the xCELLigence RTCA assays, we found that the secreted metabolites of all three halophilic strains expressed cytotoxicity to the ovarian cancer cell lines, especially A2780, as well as its cisplatin-resistant derivative A2780cis, in a dose-dependent manner. The other tested cell lines A549, HepG2, SK-OV-3 and HeLa were only minimally, or not at all affected by the archaeal metabolites, and this was only seen with the MTT assay. Conclusions The halophilic archaea Hrd. rudnickae and Nnm. salaciae, isolated from a Polish salt mine and Lake Medee in the Mediterranean Sea, respectively, secrete metabolites that are active against ovarian cancer cells, including those that are resistant to cisplatin. This opens potential new possibilities for the treatment of these frequent and deadly gynaecological cancers

Carboranyl-1,8-naphthalimide intercalators induce lysosomal membrane permeabilization and ferroptosis in cancer cell lines

The synthesis of carborane-1,8-naphthalimide conjugates and evaluation of their DNA-binding ability and anticancer activity were performed. A series of 4-carboranyl-3-nitro-1,8-naphthalimide derivatives, mitonafide and pinafide analogs, were synthesised via amidation and reductive amination reactions, and their calf thymus DNA (ct-DNA)-binding properties were investigated using circular dichroism, UV–vis spectroscopy, and thermal denaturation. Results showed that conjugates 34–37 interacted very strongly with ct-DNA (ΔTm = 10.00–13.00 °C), indicating their ability to intercalate with DNA, but did not inhibit the activity of topoisomerase II. The conjugates inhibited the cell growth of the HepG2 cancer cell line in vitro. The same compounds caused the G2M phase arrest. Cell lines treated with these conjugates showed an increase in reactive oxygen species, glutathione, and Fe2+ levels, lipid peroxidation, and mitochondrial membrane potential relative to controls, indicating the involvement of ferroptosis. Furthermore, these conjugates caused lysosomal membrane permeabilization in HepG2 cells but not in MRC-5 cells.</p