Anti-AIDS agents 89. Identification of DCX derivatives as anti-HIV and chemosensitizing dual function agents to overcome P-gp-mediated drug resistance for AIDS therapy.

  title={Anti-AIDS agents 89. Identification of DCX derivatives as anti-HIV and chemosensitizing dual function agents to overcome P-gp-mediated drug resistance for AIDS therapy.},
  author={Ting Zhou and Emika Ohkoshi and Qian Shi and Kenneth F. Bastow and Kuo Hsiung Lee},
  journal={Bioorganic \& medicinal chemistry letters},
  volume={22 9},
In this study, 19 dicamphanoyl-dihydropyranochromone (DCP) and dicamphanoyl-dihydropyranoxanthone (DCX) derivatives, previously discovered as novel anti-HIV agents, were evaluated for their potential to reverse multi-drug resistance (MDR) in a cancer cell line over-expressing P-glycoprotein (P-gp). Seven compounds fully reversed resistance to vincristine (VCR) at 4 μM, a 20-fold enhancement compared to the first generation chemosensitizer, verapamil (4 μM). The mechanism of action of DCPs and… Expand
Recent insight into the biological activities of synthetic xanthone derivatives.
  • Shagufta, I. Ahmad
  • Chemistry, Medicine
  • European journal of medicinal chemistry
  • 2016
This review has compiled and discussed recent developments on the pharmacological profile of synthetic xanthone derivatives for different therapeutic targets and offers support in the development of new xanthones derivatives as therapeutic agents. Expand


Anti-AIDS agents 79. Design, synthesis, molecular modeling and structure-activity relationships of novel dicamphanoyl-2',2'-dimethyldihydropyranochromone (DCP) analogs as potent anti-HIV agents.
Quantitative structure-activity relationship (QSAR) modeling results were first performed on this compound type, and the models should aid in design of future anti-HIV DCP analogs and potential clinical drug candidates. Expand
Anti-AIDS agents 85. Design, synthesis, and evaluation of 1R,2R-dicamphanoyl-3,3-dimethyldihydropyrano-[2,3-c]xanthen-7(1H)-one (DCX) derivatives as novel anti-HIV agents.
Structural-activity relationship information suggested that the extended conjugated system of the pyranoxanthone skeleton facilitates the interaction of the small DCX molecule within the viral binding pocket, consequently leading to enhanced anti-HIV activity and selectivity. Expand
Overexpression of glucosylceramide synthase and P-glycoprotein in cancer cells selected for resistance to natural product chemotherapy.
It is concluded that selection pressure for resistance to natural product chemotherapy drugs selects for enhanced ceramide metabolism through glucosylceramide synthase in addition to enhanced P-gp expression. Expand
Structure of P-Glycoprotein Reveals a Molecular Basis for Poly-Specific Drug Binding
P-glycoprotein detoxifies cells by exporting hundreds of chemically unrelated toxins but has been implicated in multidrug resistance (MDR) in the treatment of cancers and a structural description of poly-specific drug-binding is important for the rational design of anticancer drugs and MDR inhibitors. Expand
Effects of chemopreventive citrus phytochemicals on human P-glycoprotein and multidrug resistance protein 1.
The results suggest that chemopreventive citrus phytochemicals, such as nobiletin found in oranges, have inhibitory effects on P-glycoprotein and/or MRP1, and may cause food-drug interactions. Expand
Induction of P‐glycoprotein expression and activity by ritonavir in bovine brain microvessel endothelial cells
Extended exposure of BMEC to ritonavir caused a concentration‐dependent increase in P‐gp activity and expression, giving insight into the central nervous system as an HIV sanctuary site and eventual development of HIV dementia. Expand
Quantitation of Doxorubicin Uptake, Efflux, and Modulation of Multidrug Resistance (MDR) in MDR Human Cancer Cells
Direct in vitro and in vivo information is added on the capacity of the transporter protein Pgp to efflux doxorubicin and on the reversal of MDR by Pgp inhibitors in resistant cancer cells. Expand
Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis).
It is concluded that the binding affinity of the drugs depends on the number of the pharmacophore points simultaneously involved in the interaction with P-gp, and it is proposed that different drugs can interact with different receptor points in different binding modes. Expand
Phenotypic instability of drug sensitivity in a human colon carcinoma cell line.
Some human colon tumors may be phenotypically unstable with respect to drug sensitivity, and this could contribute to clinical resistance to chemotherapeutic compounds. Expand
Spectral analysis of doxorubicin accumulation and the indirect quantification of its DNA intercalation.
  • O. Hovorka, V. Šubr, +7 authors B. Říhová
  • Chemistry, Medicine
  • European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V
  • 2010
To analyze influx and nuclear accumulation of Dox (free or polymer-bound) by flow cytometry, this work proposes using an indirect method based on its DNA intercalation competition with Hoechst 33342 rather than a direct measurement of doxorubicin fluorescence inside the cells. Expand