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Multidrug resistance (MDR) is a common phenomenon in clinical oncology, whereby cancer cells become resistant to chemotherapeutic drugs. A common MDR mechanism is the overexpression of ATP-binding cassette efflux transporters in cancer cells, with P-glycoprotein (P-gp) being one of them. New 3,4-seco-lupane triterpenoids, and the products of their intramolecular cyclization with the removed 4,4-gem-dimethyl group, were synthesized by the selective transformations of the A-ring of dihydrobetulin. Among the semi-synthetic derivatives, the MT-assay-enabled methyl ketone 31 (MK), exhibiting the highest cytotoxicity (0.7–16.6 µM) against nine human cancer cell lines, including P-gp overexpressing subclone HBL-100/Dox, is identified. In silico, MK has been classified as a potential P-gp-inhibitor; however, the Rhodamine 123 efflux test, and the combined use of P-gp-inhibitor verapamil with MK in vitro, showed the latter to be neither an inhibitor nor a substrate of P-gp. As the studies have shown, the cytotoxic effect of MK against HBL-100/Dox cells is, arguably, induced through the activation of the ROS-mediated mitochondrial pathway, as evidenced by the positive Annexin V-FITC staining of apoptotic cells, the cell cycle arrest in the G0/G1 phase, mitochondrial dysfunction, cytochrome c release, and the activation of caspase-9 and -3.

Laser interference microscopy (LIM) is a promising label-free method for single-cell research applicable to cell viability assessment in the studies of mammalian cells. This paper describes the development of a sensitive and reproducible method for assessing cell viability using LIM. The method, based on associated signal processing techniques, has been developed as a result of real-time investigation in phase thickness fluctuations of viable and non-viable MCF-7 cells, reflecting the presence and absence of their metabolic activity. As evinced by the values of the variable vc, this variable determines the viability of a cell only in the attached state (vc exceeds 20 nm2 for viable attached cells). The critical value of the power spectrum slope βc of the phase thickness fluctuations equals 1.00 for attached MCF-7 cells and 0.71 for suspended cells. The slope of the phase fluctuations’ power spectrum for MCF-7 cells was determined to exceed the threshold value of βc for a living cell, otherwise the cell is dead. The results evince the power spectrum slope as the most appropriate indicator of cell viability, while the integrated evaluation criterion (vc and βc values) can be used to assay the viability of attached cells.

No abstract

An efficient one-pot synthesis of the cis-pyridylimine palladium (II) complexes is reported. The compo- sition and structure were proved by NMR, IR, X-ray, and elemental analysis. The monoamine oxidase inhibition activity of synthesized complexes, including six complexes previously unknown, were inves- tigated on native mouse brains. Some of the synthesized compounds: cis-dichlorido-2,6-dimethyl-N- ((pyridin-2-yl)methylene)anilinepalladium(II), cis-dichlorido-4-nitro-N-((pyridin-2-yl)methylene)- anilinepalladium(II), and cis-dibromido-2,6-di(propan-2-yl)-N-((pyridin-2-yl)methylene)aniline- palladium(II) inhibited monoamine oxidase with moderate activity (IC50: 13.09–17.66 μМ). None of the studied compounds showed cytotoxic activity against HEK-293 cell line (human kidney embryonic cells). Acute systemic toxicity assay, that is conducted by intraperitoneal injection of cis-dichlorido-4- nitro-N-((pyridin-2-yl)methylene)anilinepalladium(II) indicated low toxicity (LD50> 5000 mg / kg) for outbred stocks mice. Bioavailability was assessed by logP’s measurement.