Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells

Guilherme L. Indig, Gregory S. Anderson, Michael G. Nichols, Jeremy A. Bartlett, William S. Mellon, Fritz Sieber

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Extensively conjugated cationic molecules with appropriate structural features naturally accumulate into the mitochondria of living cells, a phenomenon typically more prominent in tumor than in normal cells. Because a variety of tumor cells also retain pertinent cationic structures for longer periods of time compared with normal cells, mitochondrial targeting has been proposed as a selective therapeutic strategy of relevance for both chemotherapy and photochemotherapy of neoplastic diseases. Here we report that the triarylmethane dye crystal violet stains cell mitochondria with efficiency and selectivity, and is a promising candidate for photochemotherapy applications. Crystal violet exhibits pronounced phototoxicity toward L1210 leukemia cells but comparatively small toxic effects toward normal hematopoietic cells (murine granulocyte-macrophage progenitors, CFU-GM). On the basis of a comparative examination of chemical, photochemical, and phototoxic properties of crystal violet and other triarylmethane dyes, we have identified interdependencies between molecular structure, and selective phototoxicity toward tumor cells. These structure- activity relationships represent useful guidelines for the development of novel purging protocols to promote selective elimination of residual tumor cells from autologous bone marrow grafts with minimum toxicity to normal hematopoietic stem cells. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)88-99
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume89
Issue number1
DOIs
StatePublished - Jan 2000
Externally publishedYes

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Bone Marrow Purging
Purging
Residual Neoplasm
Molecular Structure
Gentian Violet
Grafts
Molecular structure
Tumors
Bone
Coloring Agents
Cells
Transplants
Mitochondria
Phototoxic Dermatitis
Granulocyte-Macrophage Progenitor Cells
Photochemotherapy
Chemotherapy
Macrophages
Poisons
Therapeutics

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Effect of molecular structure on the performance of triarylmethane dyes as therapeutic agents for photochemical purging of autologous bone marrow grafts from residual tumor cells. / Indig, Guilherme L.; Anderson, Gregory S.; Nichols, Michael G.; Bartlett, Jeremy A.; Mellon, William S.; Sieber, Fritz.

In: Journal of Pharmaceutical Sciences, Vol. 89, No. 1, 01.2000, p. 88-99.

Research output: Contribution to journalArticle

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