Comparison of the cytotoxic effect of lapachol, α-lapachone and pentacyclic 1,4-naphthoquinones on human leukemic cells

Abstract

The pentacyclic 1,4-naphthoquinones 1a-d were cytotoxic (IC(50) approximately 2-7 microM) to human leukemic cell lines K562 (oxidative stress-resistant), Lucena-1 (MDR phenotype) and Daudi. Fresh leukemic cells obtained from patients, some with the MDR phenotype, were also sensitive to these compounds. The pentacyclic 1,4-naphthoquinones 1a and 1c induced apoptotic cell death in cells from leukemic patients as determined by flow cytometry. Conversely, the cell lines were highly insensitive to lapachol (2) and alpha-lapachone (3). Mitomycin-C inhibited cell proliferation at concentrations as low as 0.5 microM. The low toxicity against lymphocytes activated by phytohemagglutinin shows that these compounds are selective for the cancer cells studied. Previous data suggest that these compounds (1a-d) can be bioactivated in situ by reduction followed by rearrangement leading to enones, which are powerful alkylating agents. In contrast, lapachol (2) and beta-lapachone (3), which cannot be bioactivated by reduction, showed little activity against the same cell lines.

Natural and Synthetic Naphthoquinones Active Against Trypanosoma Cruzi: An Initial Step Towards New Drugs for Chagas Disease

“…Last year several, -lapachone derivatives were synthesized and their biological properties evaluated [66,[106][107][108]. Although -isomers were found more active, there are examples indicating that some structural modifications produce -lapachone derivatives with interesting anti-trypanosoma properties [68].…”

Self-sterility in the hexaploid Handroanthus serratifolius (Bignoniaceae), the national flower of Brazil

“…Due to its ubiquity and beauty, the species was designated the national flower of Brazil and is the emblem of the Brazilian Botanical Society (Gentry 1992b). In addition to its ornamental value (Lorenzi 1992), the species is important for the timber industry, as well as for the pharmaceutical industry, which uses it for a variety of purposes (Gentry 1992a, Lorenzi 1992, including cancer-related research (Oliveira et al 2002;Salustiano et al 2010). This species is reportedly hexaploid, with 2n=120 chromosomes, presenting monoembryonic populations (Sampaio 2010) and populations with high percentages of polyembryonic seeds (Mendes-Rodrigues et al 2012).…”

New pterocarpanquinones: Synthesis, antineoplasic activity on cultured human malignant cell lines and TNF-α modulation in human PBMC cells

“…These compounds can also be seen as analogs of Kalafungin, an antimicrobial agent obtained from the culture broth of a soil isolate of Streptomyces tanashiensis, sharing in their structures the dihydrofuran moiety. 21,22 Pterocarpanquinones 4a-g were synthesized and presented antineoplasic effect on human leukemic cell lines mentioned above 23 and MCF-7 breast cancer cell line. 24 Some of these pterocarpanquinones were also active in fresh leukemic cell samples obtained from patients and overexpressing ATP-binding cassette transporters (ABC) proteins.…”

“…24 Some of these pterocarpanquinones were also active in fresh leukemic cell samples obtained from patients and overexpressing ATP-binding cassette transporters (ABC) proteins. 23 On the other hand, these pterocarpanquinones showed low cytotoxicity to peripheral blood mononuclear cells (PBMC) activated by PHA. 23 While in MCF-7 cells the antineoplasic activity was stronger for compounds bearing a phenol group at the E ring, the antileukemic profile was independent on the oxygenation pattern at this ring.…”

“…23 On the other hand, these pterocarpanquinones showed low cytotoxicity to peripheral blood mononuclear cells (PBMC) activated by PHA. 23 While in MCF-7 cells the antineoplasic activity was stronger for compounds bearing a phenol group at the E ring, the antileukemic profile was independent on the oxygenation pattern at this ring. 24 So, in order to know more about the structure-activity relationships, we decided to synthesise a new derivative (5a) without substitution at the E ring.…”