Matches in SemOpenAlex for { <https://semopenalex.org/work/W1915172695> ?p ?o ?g. }
Showing items 1 to 82 of
82
with 100 items per page.
- W1915172695 endingPage "62" @default.
- W1915172695 startingPage "454" @default.
- W1915172695 abstract "Multidrug resistance (MDR), typified by resistance to Vinca alkaloids and anthracyclines, is a well characterized experimental phenomenon that may have some clinical correlates. Verapamil, chloroquine, and related drugs have been shown previously to be capable of enhancing anticancer drug cytotoxicity in multi-drug-resistant cells, but the mechanism(s) by which these agents do this is(are) unclear. Since these agents did not seem to have common features, we studied these and other compounds for their ability to modulate Vinca alkaloid resistance in order to determine whether they possessed any common chemical or physical features. In addition to verapamil, 24 compounds, consisting of indole alkaloids, lysosomotropic agents, and amines, were tested for their ability to enhance the cytotoxicity of vinblastine and/or vincristine in our human leukemic multidrug-resistant cell line, CEM/VLB100. Seventeen compounds that enhance the cytotoxicity of the Vinca alkaloids by more than 5-fold have been identified. These include quinolines (chloroquine, quinine, chinchonidine, and primaquine), acridines (acridine, acridine orange, and quinacrine), and indole alkaloids (yohimbine, corynanthine, reserpine, physostigmine, and the vindoline and catharanthine moieties of the Vinca alkaloids), as well as other alkaloids and amines (chlorpromazine, propranolol, atropine, and tryptamine). Vindoline, catharanthine, and quinacrine also enhanced the cytotoxicity of doxorubicin and teniposide in these cells, indicating that this modulation was not limited to Vinca alkaloids. We examined some well known lysosomotropic compounds (methylamine, epinephrine, suramin, and trypan blue) and found that they were not able to enhance the cytotoxicity of vincristine in the CEM/VLB100 cells, indicating that lysosomotropic activity per se is not required for modulator activity. Three-dimensional computer modeling permitted molecular comparisons of conformationally related congeners of vinblastine, vindoline, and verapamil and revealed three regions of structural homology. We measured the hydrophobicity (by oil/water partitioning) and calculated the molar refractivity (by the additive substituent constant method) of active and inactive compounds. We found that those cationic agents--verapamil, quinacrine, indole alkaloids, and quinolines--that were lipid soluble at physiologic pH and had similar molar refractivities were best able to enhance the cytotoxicity of the Vinca alkaloids in our multidrug-resistant cells.(ABSTRACT TRUNCATED AT 400 WORDS)" @default.
- W1915172695 created "2016-06-24" @default.
- W1915172695 creator A5014700401 @default.
- W1915172695 creator A5059498891 @default.
- W1915172695 creator A5069785780 @default.
- W1915172695 date "1988-04-01" @default.
- W1915172695 modified "2023-10-17" @default.
- W1915172695 title "Physical-chemical properties shared by compounds that modulate multidrug resistance in human leukemic cells." @default.
- W1915172695 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/3162758" @default.
- W1915172695 hasPublicationYear "1988" @default.
- W1915172695 type Work @default.
- W1915172695 sameAs 1915172695 @default.
- W1915172695 citedByCount "144" @default.
- W1915172695 countsByYear W19151726952012 @default.
- W1915172695 countsByYear W19151726952013 @default.
- W1915172695 countsByYear W19151726952014 @default.
- W1915172695 countsByYear W19151726952015 @default.
- W1915172695 countsByYear W19151726952016 @default.
- W1915172695 countsByYear W19151726952017 @default.
- W1915172695 countsByYear W19151726952018 @default.
- W1915172695 countsByYear W19151726952022 @default.
- W1915172695 crossrefType "journal-article" @default.
- W1915172695 hasAuthorship W1915172695A5014700401 @default.
- W1915172695 hasAuthorship W1915172695A5059498891 @default.
- W1915172695 hasAuthorship W1915172695A5069785780 @default.
- W1915172695 hasConcept C109316439 @default.
- W1915172695 hasConcept C133936738 @default.
- W1915172695 hasConcept C178790620 @default.
- W1915172695 hasConcept C185592680 @default.
- W1915172695 hasConcept C202751555 @default.
- W1915172695 hasConcept C2776694085 @default.
- W1915172695 hasConcept C2777022698 @default.
- W1915172695 hasConcept C2777096885 @default.
- W1915172695 hasConcept C2777132456 @default.
- W1915172695 hasConcept C2777621752 @default.
- W1915172695 hasConcept C2777667214 @default.
- W1915172695 hasConcept C501593827 @default.
- W1915172695 hasConcept C519063684 @default.
- W1915172695 hasConcept C54355233 @default.
- W1915172695 hasConcept C55493867 @default.
- W1915172695 hasConcept C71240020 @default.
- W1915172695 hasConcept C86803240 @default.
- W1915172695 hasConcept C98274493 @default.
- W1915172695 hasConceptScore W1915172695C109316439 @default.
- W1915172695 hasConceptScore W1915172695C133936738 @default.
- W1915172695 hasConceptScore W1915172695C178790620 @default.
- W1915172695 hasConceptScore W1915172695C185592680 @default.
- W1915172695 hasConceptScore W1915172695C202751555 @default.
- W1915172695 hasConceptScore W1915172695C2776694085 @default.
- W1915172695 hasConceptScore W1915172695C2777022698 @default.
- W1915172695 hasConceptScore W1915172695C2777096885 @default.
- W1915172695 hasConceptScore W1915172695C2777132456 @default.
- W1915172695 hasConceptScore W1915172695C2777621752 @default.
- W1915172695 hasConceptScore W1915172695C2777667214 @default.
- W1915172695 hasConceptScore W1915172695C501593827 @default.
- W1915172695 hasConceptScore W1915172695C519063684 @default.
- W1915172695 hasConceptScore W1915172695C54355233 @default.
- W1915172695 hasConceptScore W1915172695C55493867 @default.
- W1915172695 hasConceptScore W1915172695C71240020 @default.
- W1915172695 hasConceptScore W1915172695C86803240 @default.
- W1915172695 hasConceptScore W1915172695C98274493 @default.
- W1915172695 hasIssue "4" @default.
- W1915172695 hasLocation W19151726951 @default.
- W1915172695 hasOpenAccess W1915172695 @default.
- W1915172695 hasPrimaryLocation W19151726951 @default.
- W1915172695 hasRelatedWork W1547342210 @default.
- W1915172695 hasRelatedWork W1645667097 @default.
- W1915172695 hasRelatedWork W1915172695 @default.
- W1915172695 hasRelatedWork W1963779461 @default.
- W1915172695 hasRelatedWork W2002201523 @default.
- W1915172695 hasRelatedWork W2065723669 @default.
- W1915172695 hasRelatedWork W2134450673 @default.
- W1915172695 hasRelatedWork W2159772102 @default.
- W1915172695 hasRelatedWork W2332846877 @default.
- W1915172695 hasRelatedWork W2437473820 @default.
- W1915172695 hasVolume "33" @default.
- W1915172695 isParatext "false" @default.
- W1915172695 isRetracted "false" @default.
- W1915172695 magId "1915172695" @default.
- W1915172695 workType "article" @default.