Horisfieldones A and B, Two Aromatic Ring-Contracted Dimeric Diarylpropanes with Human DOPA Decarboxylase Inhibitory Activity from Horsfieldia kingii.

Horisfieldones A (1) and B (2), two dimeric diarylpropanes featuring an unprecedentedly aromatic ring-contracted framework, were isolated from Horsfieldia kingii. Their structures and absolute configurations were determined by the inspection of extensive spectroscopic data and electronic circular dichroism calculations. Molecular modeling analysis, in vitro enzyme-based bioassays, and structure-activity relationship analysis of these isolates revealed that (+)-1 (IC50 = 35.1 ± 3.9 µM, SI > 11.4) could present a new class of human DOPA decarboxylase inhibitor.

DOPA decarboxylase is essential for cuticle tanning in Rhodnius prolixus (Hemiptera: Reduviidae), affecting ecdysis, survival and reproduction.

Cuticle tanning occurs in insects immediately after hatching or molting. During this process, the cuticle becomes dark and rigid due to melanin deposition and protein crosslinking. In insects, different from mammals, melanin is synthesized mainly from dopamine, which is produced from DOPA by the enzyme DOPA decarboxylase. In this work, we report that the silencing of the RpAadc-2 gene, which encodes the putative Rhodnius prolixus DOPA decarboxylase enzyme, resulted in a reduction in nymph survival, with a high percentage of treated insects dying during the ecdysis process or in the expected ecdysis period. Those treated insects that could complete ecdysis presented a decrease in cuticle pigmentation and hardness after molting. In adult females, the knockdown of AADC-2 resulted in a reduction in the hatching of eggs; the nymphs that managed to hatch failed to tan the cuticle and were unable to feed. Despite the failure in cuticle tanning, knockdown of the AADC-2 did not increase the susceptibility to topically applied deltamethrin, a pyrethroid insecticide. Additionally, our results showed that the melanin synthesis pathway did not play a major role in the detoxification of the excess (potentially toxic) tyrosine from the diet, an essential trait for hematophagous arthropod survival after a blood meal.

Suppression of L-dopa-induced circling in rats with nigral lesions by blockade of central dopa-decarboxylase: implications for mechanism of action of L-dopa in parkinsonism.

Dopamine (DA) elevations in rat striatum produced by combined administration of L-dopa and carbidopa were abolished when L-dopa was injected with NSD-1015, an inhibitor of central dopa-decarboxylase. In all rats with unilateral 6-OH-DA nigral lesions, L-dopa-induced contraversive circling occurred after carbidopa, but was totally abolished (in 60%) or markedly suppressed after pretreatment with NSD-1015. Administration of the DA metabolites DOPAC and HVA systemically and of 3-methoxytyramine intrastriatally evoked no circling in animals with 6-OH-DA lesions. In rats with unilateral nigrotomies, the direction of L-dopa-induced circling was reversed and became ipsiversive after DA receptors were reduced by the addition of kainic acid lesions in ipsilateral striata. Findings provide evidence that circling in rats--and by analogy, efficacy in parkinsonians--requires the decarboxylation of exogenous L-dopa and interaction of the formed DA with DA receptors in striatum.