Selected secondary metabolites from the Phytolaccaceae and their biological/pharmaceutical significance.

Publication Type

Journal contribution (peer reviewed)

Authors

Williams, L. A. D.; Roesner, H.; Conrad, J.; Moeller, W.; Beifuss, U.; Chiba, K.; Nkurunziza, J. P.; Kraus, W.

Year of publication

2002

Published in

Recent Research Developments in Phytochemistry

Band/Volume

nn/6

ISBN / ISSN / eISSN

81-7736-195-3

Page (from - to)

13-68

The data presented within this review reveals that the Phytolaccaceous secondary metabolites belong to diverse structural classes with the ability of modulating a broadspectrum of physiological receptors, and could be explored as the following drug prototypes: anti-microbials, adenosine A₁ receptor antagonists for anti-diabetic or cardio-protective drugs, immunochemo therapeutics as anti-viral mitogens, immunocytotoxic recombinant conjugates for treating HIV, herpes and cancers and agrochemicals. In order to highlight the pharmaceutical potentials of these compounds the authors selected one of the secondary metabolites of Petiveria alliacea, dibenzyl trisulphide (DTS) which they previously revealed to be an anti-proliferative/cytotoxic agent with the ability of modulating the immune system, possible by a cytokine switching mechanism from the Th-1 to the Th-2 cytokine dominance as revealed by its dose dependent selective up-regulation of IL-4, IL-5 and IL-10 and suppression of INF-g and IL-2 (Th-1) in murine CD3 cytokine activation and Mixed Lymphocytes Response Assays, along with an activation of reticuloendothelial system parameters e.g. elevation of granulocytes counts.  In addition, Williams et al., [1] revealed that DTS is capable of increasing murine thymic and Peyer’s patches weights, without altering splenic mass and histology, while our embryonic protein synthesis studies in the zygotes of Asternia pectinifera revealed that DTS is not toxic at 10 mM on this critical life process. The IC₅₀ values found for DTS on human 5637 primary bladder carcinoma and SH-SY5Y neuroblastoma tumour were 5.24 µg/mL and 120 ng/mL, respectively. From our subcellular mechanistic studies of DTS in two well-established neuronal cell-and-tissue culture systems; in the neuroblastoma cells system, DTS attenuates the dephosphorylation of tyrosyl-residues of MAPkinases (erk1/erk2), with a reversible disassemble of microtubles, with no effects on actin dynamics in the human neuroblastoma cells and Wistar-38 lung fibroblast. The DTS stabilized heat induced immunogenic bovine serum albumin (BSA) in a pH dependent manner in vitro. 1D NMR techniques were applied to the binding/interactions between DTS and BSA, DTS and human RBC in order to support our view of DTS strong tyrosyl receptor motifs (ITAMs) binding activation mode of activating the mitogenic signal transduction pathway [2]. Conjugating DTS to BSA enhanced the molecule’s cytotoxic effects by 70 fold at 78 ng/mL on the neuroblastoma cells.