Antimicrobial, Anticancer and Multidrug-Resistant Reversing Activity of Novel Oxygen-, Sulfur- and Selenoflavones and Bioisosteric Analogues

Abstract

Multidrug resistance of cancer cells to cytotoxic drugs still remains a major obstacle to the success of chemotherapy in cancer treatment. The development of new drug candidates which may serve as P-glycoprotein (P-gp) efflux pump inhibitors is a promising strategy. Selenium analogues of natural products, such as flavonoids, offer an interesting motif from the perspective of drug design. Herein, we report the biological evaluation of novel hybrid compounds, bearing both the flavone core (compounds 1–3) or a bioisosteric analogue core (compounds 4–6) and the triflyl functional group against Gram-positive and Gram-negative bacteria, yeasts, nematodes, and human colonic adenocarcinoma cells. Results show that these flavones and analogues of flavones inhibited the activity of multidrug resistance (MDR) efflux pump ABCB1 (P-glycoprotein, P-gp). Moreover, the results of the rhodamine 123 accumulation assay demonstrated a dose-dependent inhibition of the abovementioned efflux pump. Three compounds (4, 5, and 6) exhibited potent inhibitory activity, much stronger than the positive control, verapamil. Thus, these chalcogen bioisosteric analogues of flavones become an interesting class of compounds which could be considered as P-gp efflux pump inhibitors in the therapy of MDR cancer. Moreover, all the compounds served as promising adjuvants in the cancer treatment, since they exhibited the P-gp efflux pump modulating activity.

Triterpenes from Pholiota populnea as Cytotoxic Agents and Chemosensitizers to Overcome Multidrug Resistance of Cancer Cells

“…In particular, ATP-binding cassette (ABC) transporters have received great interest; one such transporter that has been investigated in detail is P-glycoprotein (P-gp). 2 Triterpenoids were reported to be able to reverse cell resistance to chemotherapy due to P-gp inhibition. Ginsenoside Rh2, isolated from red ginseng, exerts such activity in doxorubicin-resistant human breast cancer MCF-7 cells.…”

“…One of the most widespread mechanisms of resistance involves the efflux of drug molecules out of the cells. In particular, ATP-binding cassette (ABC) transporters have received great interest; one such transporter that has been investigated in detail is P-glycoprotein (P-gp) . Triterpenoids were reported to be able to reverse cell resistance to chemotherapy due to P-gp inhibition.…”

Radical cyclization of alkynyl aryl ketones for the synthesis of 3-seleno-substituted thiochromones and chromones

“…MS (rel. int 4,159.8,134.8,133.1,127.0,120.3,112.3,95.6,81.9,56.0,31.2,27.7,22.3,19.4,14.1. MS (rel.…”

“…77 1, 157.1, 138.3, 137.3, 131.8, 130.4, 130.1, 129.8, 128.5, 128.4, 128.3, 127.4, 126.4, 125.7, 121.7, 121.5, 110.5, 55.8. 77 ), 155.5, 138.1, 137.4, 135.0 (d, 3 J C-F = 7.9 Hz),131.9,129.9,129.87,129.8,128.8,128.7,128.5,128.3,126.3 (d,4 J C-F = 3.4 Hz),125.7,116.1 (d,2 J C-F = 21.5 Hz). 77 Se{ 1 H} NMR (CDCl 3 , 76 MHz) δ ( ppm) = 350.5.…”

“…2 For example, the thiochromone scaffold is present in molecules showing human monoamine oxidase B ( h MAO-B) inhibitory activity (Fig. 1, compound A ) 3 and anticancer activity 4 (Fig. 1, compound B ).…”