Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro

“…Following the predetermined intervals of 12, 24 and 48 h, the cultures were incubated with MTT (0.44 umol) for 5 h (Lu et al, 2004, Orfila et al, 2000and Gerlier and Thomasset, 1986. The degree of formazan formation was determined by rinsing the wells with HBSS prior to the addition of 50 μl of DMSO and subsequent reading on a Varion spectrophotometer at 570 nm (1 cm path length).…”

Section: Toxicity Assaymentioning

confidence: 99%

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

Naidoo

Swan

2009

Comparative Biochemistry and Physiology Part C: Toxicology &

View full text Add to dashboard Cite

show abstract

“…This specu- lation might also be supported by our unpublished findings that several other derivatives synthesized by further modifications of berberine specifically inhibit the activity of other kinases in S. pombe MAPK cascades other than Wis1. 2 Further investigation into the specific binding modes of berberine derivatives to kinases will provide clues about how to develop specific inhibitors against distinct members of MAP kinase cascades by additional modification.…”

Section: Noncovalent But Strong Binding Of Hwy 289 and Hwy 336 To Wismentioning

confidence: 99%

Selective Inhibition of MAPKK Wis1 in the Stress-activated MAPK Cascade of Schizosaccharomyces pombe by Novel Berberine Derivatives

Jang

Jwa

Kim

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

Berberine alkaloids supposedly have diverse biological effects including anti-tumor activity in mice, anti-Candida activity, cytotoxic activities against human cancer cell lines, and inhibition of dopamine biosynthesis (1-4); however, their cytotoxic targets and biological mechanisms have yet to be identified. Since berberine has been shown to inhibit the growth of Candida albicans, Candida glabrata, and Candida tropicalis, 515 synthetic and semisynthetic berberine derivatives were produced and screened for more effective anti-fungal activity in C. albicans (5). C. albicans is the most frequently isolated fungal pathogen in humans. Its ability to change from a yeast form to a filamentous hypal or pseudohypal form during growth is thought to contribute to its virulence (6). HWY 289 and HWY 336 were selected because of their highly effective anti-Candida properties in the screen. Since C. albicans is a diploid fungus with no known sexual cycle and target validation by genetic approaches is limited, direct targets of HWY 289 and HWY 336 were identified in the fission yeast Schizosaccharomyces pombe, which is amenable for genetic studies. Studies using various mutations of the budding yeast S. cerevisiae have shown that yeast provides a good system for identifying targets of known compounds such as rapamycin and FK506 (7,8). Recently, the usage of budding yeast Saccharomyces cerevisiae has been expanded to include screenings for valuable chemical compounds or peptides for anticancer drugs and protein kinase inhibitors (9 -12). In this paper, we report that the novel berberine derivatives having anti-Candida properties, HWY 289 and HWY 336, selectively inhibit the in vivo and in vitro activities of a specific kinase in the stress-activated mitogen-activated protein kinase (MAPK) 1 cascade in S. pombe. MAPK (sometimes called extracellular signal-regulated kinase (ERK)) cascades are highly conserved signaling cassettes found in all eukaryotes. Eukaryotic cells respond to diverse extracellular stimuli such as growth factors, hormones, high temperature, osmotic shock, and hydroxyl radicals by activating distinct MAP kinase cascades, which lead to diverse regulatory events including proliferation, differentiation, and cell death. Therefore, kinases in distinct MAPK cascades serve as effective cytotoxic targets for a number of anti-fungal, antitumor, and anti-inflammatory drugs. Each MAPK cascade is composed of a series of three or more protein kinases, each phosphorylating, thereby activating, the next kinase in the pathway. MAPKs are activated by phosphorylation at conserved threonine and tyrosine residues in the catalytic domain by MAPK kinases (MAPKKs, sometimes called MEKs). These are in turn activated by phosphorylation of specific conserved serine/threonine residues by MAPK kinase kinases (MAPKKKs, sometimes called MEKKs). Several MAPK cascades exist in a cell. Each of them functions in parallel by mediating

show abstract

Structural modification of berberine alkaloids in relation to cytotoxic activity in vitro

Cited by 54 publications

References 12 publications

Antiproliferative Activity of Vietnamese Medicinal Plants.

Antiproliferative Activity of Vietnamese Medicinal Plants.

Diclofenac toxicity in Gyps vulture is associated with decreased uric acid excretion and not renal portal vasoconstriction

Selective Inhibition of MAPKK Wis1 in the Stress-activated MAPK Cascade of Schizosaccharomyces pombe by Novel Berberine Derivatives

Contact Info

Product

Resources

About