Background/Aim: This study examined the potential role of natural triterpenoids lupeol, calenduladiol and heliantriol B2, and a set of 19 derivatives, as antiproliferative and antimetastatic agents against prostate cancer cells. Materials and Methods: Natural triterpenoids were isolated from Chuqiraga erinaceae. Analogs were obtained by transformations of lupeol and calenduladiol. The effects of compounds on PC-3 and LNCaP cells were determined using the MTT assay. Compounds with half-maximal inhibitory concentration <70 μM were evaluated as antimetastatic agents by a wound-healing assay. Results: Lupeol-3β-sulfate, a new semisynthetic lupane, was the most active compound. In general, sulfated derivatives displayed higher activity than the lead against both cell lines. A new analog, calenduladiol-3β-monosulfate, inhibited the migration of PC-3 cells; heliantriol B2 and 3β-aminolupane inhibited the migration of LNCaP cells in a concentration-dependent manner. Conclusion: Our study provides novel agents with cytotoxic effects on prostate cancer cells, which may represent a potential new therapeutic approach for prostate cancer.

Polyphenols are attracting increasing attention in the discovery of useful agents for the treatment of neurodegenerative diseases. Thelesperma megapotamicum (Spreng.) Kuntze belongs to the family Asteraceae, which is known to have a high antioxidant capacity. The phytochemical investigation of T. megapotamicum revealed the presence of 1′-S-isobutyroxyeugenol isobutyrate, (1), lupeol, (2), 1′-S-acetoxyeugenol isobutyrate, (3), stigmasterol, (4), β-sitosterol, (5), eriodictyol, (6), luteolin, (7), and marein, (8), as major secondary metabolites. The neuroprotective activity of this species was studied by evaluating the inhibition in vitro of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), and the antioxidant capacity of the sub-extracts and of the major metabolites isolated from them. The AChE and BChE inhibition were determined by Ellman’s method and the antioxidant activity by DPPH assay. The inhibitory activity against BChE and the antioxidant capacity of the polyphenols present in T. megapotamicum highlight this species as a promising source of active metabolites for the development of agents for the treatment of neurodegenerative diseases.

Helminthiasis is a serious problem worldwide resulting in high human morbidity and enormous economic losses in livestock, especially in tropical and sub-tropical countries. Anthelmintic drugs are used for the control of parasitic infections caused by helminths. Resistance to current anthelmintics has prompted the search for new drugs. In this context, the tricyclic dibenzo[b,e]oxepin-11(6H)-one scaffold emerges as an interesting synthetic target because a large number of compounds having this privileged structure present relevant biological activities; such as antidepressant, anxiolytic, antipsychotic, antitumor, and anti-inflammatory properties. Herein, we describe the development of first systematic study for the generation of a small library of dibenzo[b,e]oxepin-11(6H)-ones by direct intramolecular acylation from readily available 2-(phenoxymethyl)benzoic acids. For this purpose, a novel and efficient cooperative system consisting of SnCl₂ and Cl₂CHOCH₃ (DCME) is presented. This new methodology show be compatible with a wide variety of functional groups in good to excellent yields and high regioselectivity. The generality of present protocol was applied to the scalable and reproducible synthesis of tricyclic antidepressant doxepin. The synthesized dibenzo[b,e]oxepinones were evaluated for their biological activity using the free-living nematode Caenorhabditis elegans as effective and cost-efficient model system for anthelmintic discovery.

According to the cholinergic hypothesis, the inhibition of cholinesterase increases the levels of acetylcholine in the brain, thus improving cholinergic functions in Alzheimer´s Disease (AD) patients. Butyrylcholinesterase (BChE), is one of the enzymes involved in the metabolic degradation of acetylcholine, together with acetylcholinesterase (AChE). BChE activity increases as AD progresses, which suggests that BChE may play an important role at the latter stages of AD. Therefore, selective BChE inhibitors attract interest nowadays.Lup-20(29)-ene-3β,16β-diol (calenduladiol, 1), is a pentacyclic lupane-type triterpene with the interesting feature of being hydroxylated at C-16. Continuing our previous work on semisynthesis of derivatives obtained from the natural triterpene calenduladiol and their evaluation as potential cholinesterase inhibitors, we report here the synthesis of six new lupanes (3-8). These compounds have been obtained by sequential oxidations and reaction with NH₂OH of the starting compounds, the natural calenduladiol (1) and its analog 30-oxocalenduladiol (2), previously obtained by allylic oxidation with Se₂O. Their structures were confirmed by analysis of their 1H and 13C NMR and ESI-MS spectra. The complete assignation of the signals was achieved with the aid of 2D NMR experiments (COSY, HSQC, HMBC, NOESY). All of the new derivatives were evaluated as potential in vitro BChE inhibitors by the Ellman´s colorimetric method. In order to determine the BChE/AChE selectivity of compounds 3-8, their antiAChE activity was evaluated. All of them failed to inhibit AChE, but we found that the best BChE inhibition was observed for 3,16,30-trioxolup-20(29)-ene (4) with an IC₅₀ value of 21.5 μM, which elicited a selective inhibitor profile

Alzheimer´s disease (AD) is a progressive neurodegenerative disorder associated with memory impairment and cognitive deficit. It is characterized by low levels of the neurotransmitter acetylcholine (ACh) in the brain of AD patients. The inhibition of acetylcholinesterase (AChE), the enzyme that catalyzes ACh hydrolysis, is the main therapeutic strategy used to treat AD. In the healthy brain, another enzyme, namely butyrylcholinesterase (BChE), is involved in the metabolic degradation of ACh. BChE activity increases as AD progresses, which suggests that BChE may play an important role at the latter stages of AD. Therefore, selective BChE inhibitors attract interest nowadays. The chemistry of lupane-type triterpenoids has been actively explored due to their biological and pharmacological properties. Abundant in many plants, these metabolites are valuable natural raw materials to perform chemical modifications. In the present work, we aimed to evaluate of natural and semisynthetic lupanes as potential in vitro cholinesterase inhibitors. Lupeol (1) (lup-20(29)-en-3β-ol) and calenduladiol (2) (lup-20(29)-en-3β,16β-diol) have been isolated from Chuquiraga erinacea subsp. erinacea (Asteraceae), an endemic species growing wildly in our region. Semisynthetic lupanes 3-16 have been prepared from them. All of them failed to inhibit AChE, but we found that most of them exhibited BChE inhibition. The best BChE inhibitors were 16-oxolup-20(29)-en-3β-ol and 3,16,30-trioxolup-20(29)-ene with IC₅₀ values of 28.9 and 21.5 µM respectively, an interesting result considering that the role of BChE is more relevant as the disease progresses.

Solanum glaucophyllum is a species of the Solanaceae family that causes enzootic calcinosis by vitamin D₃ intoxication in breeding cattle grazing in Argentina. Inspired by thrusting forward the study of the biosynthetic pathway of vitamin D₃ in S. glaucophyllum, the aim of the present work is to provide knowledge of vitamin D₃ toxicity related to concentration in the mentioned species located throughout the Río Salado basin. We present the development of a reverse-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of vitamin D₃ and its hydroxylated metabolites. An exhaustive optimization of the RP-HPLC method allowed us to perform calcitriol (1α,25-(OH)₂D₃) and calcidiol (25-OHD₃) identification, both metabolites obtained by the chemical hydrolysis of S. glaucophyllum leaves starting from its hydrophilic extract. These results allow the design of a monitoring scheme for S. glaucophyllum, achieving a more selective control of this weed to avoid cattle decline in the Río Salado basin.