Merck, SMB00609-1MG, 6,6′-Dihydroxythiobinupharidine

General description
6,6′-Dihydroxythiobinupharidine is an active compound found in Nuphar lutea extract. It is a dimeric sesquiterpene thioalkaloid which presents multiple activities.
Biochem/physiol Actions
6,6′-Dihydroxythiobinupharidine inhibits NFκB activation, leading to an induction of apoptosis via cleavage of procaspase-9 and poly (ADP-ribose) polymerase (PARP).

It was also found to act synergistically with cytotoxic drugs such as cisplatin and etoposide, enabling their cytotoxic effect at lower concentrations.

6,6′-Dihydroxythiobinupharidine was found to have cytotoxic activity at a concentration of ~10 μM on human leukemia cells (U937), mouse melanoma cells (B16F10), and human fibroblasts (HT1080).

In addition, Nuphar lutea extract was effective against both Leishmania promastigote and amastigote forms (IC₅₀ = 2 ± 0.12 μg/mL; ID₅₀ = 0.65 ± 0.023 μg/mL; LD₅₀ = 2.1 ± 0.096 μg/mL, STI = 3.23). A synergistic antileishmanial activity was demonstrated with the antileishmanial drug, paromomycin.

Recently 6,6′-dihydroxythiobinupharidine was found to be active against MRSA and VRE strains with an MIC of 1-4 μg/mL. Inhibition of DNA topoisomerase IV but not DNA gyrase in S. aureus was suggested as the mechanism of action. 6,6′-Dihydroxythiobinupharidine was also shown to promote neutrophil effector bactericidal functions.