The Amaryllidaceae family is well known for its pharmacologically active alkaloids. An important approach to treat Alzheimer’s disease involves the inhibition of the enzyme acetylcholinesterase (AChE). Galanthamine, an Amaryllidaceae alkaloid, is an effective, selective, reversible, and competitive AchE inhibitor. This work was aimed at studying the alkaloid composition of four wild Argentinian Amarillydaceae species for the first time, as well as analyzing their inhibitory activity on acetylcholinesterase. Alkaloid content was characterized by means of GC-MS analysis. Chloroform basic extracts from Habranthus jamesonii, Phycella herbertiana, Rhodophiala mendocina and Zephyranthes filifolia collected in the Argentinian Andean region all contained galanthamine, and showed a strong AChE inhibitory activity (IC₅₀ between 1.2 and 2 µg/mL). To our knowledge, no previous reports on alkaloid profiles and AChEIs activity of wild Argentinian Amarillydaceae species have been publisihed. The demand for renewable sources of industrial products like galanthamine and the need to protect plant biodiversity creates an opportunity for Argentinian farmers to produce such crops.

In Argentina, the Amaryllidaceae family (59 species) comprises a wide variety of genera, only a few species have been investigated as a potential source of cholinesterases inhibitors to treat Alzheimer disease (AD). To study the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of the basic dichloromethane extracts (E) from Hieronymiella aurea, H. caletensis, H. clidanthoides, H. marginata, and H. speciosa species, as well as the isolated compounds from these plant extracts. AChE and BChE inhibitory activities were evaluated with the Ellman's spectrophotometric method. The alkaloids composition from the E was obtained by gas chromatography-mass spectrometry (GC-MS). The E were successively chromatographed on a silica gel column and permeated on Sephadex LH-20 column to afford the main alkaloids identified by means of spectroscopic data. Additionally, an in silico study was carried out. Nine known alkaloids were isolated from the E of five Hieronymiella species. Galanthamine was identified in all the species by GC-MS standing out H. caletensis with a relative abundance of 9.79% of the total ion current. Strong AChE (IC50 = 1.84 - 15.40 µg/ml) and moderate BChE (IC50 = 23.74 - 136.40 µg/ml) inhibitory activities were displayed by the extracts. Among the isolated alkaloids, only sanguinine and chlidanthine (galanthamine-type alkaloids) demonstrated inhibitory activity toward both enzymes. The QTAIM study suggests that sanguinine has the strongest affinity towards AChE, attributed to an additional interaction with Ser200 as well as stronger molecular interactions Glu199 and His440.These results allowed us to differentiate the molecular behavior in the active site among alkaloids possessing different in vitro inhibitory activities. Hieronymiella species growing in Argentina represent a rich and widespread source of galanthamine and others AChE and BChE inhibitors alkaloids. Additionally, the new trend towards the use of natural extracts as pharmaceuticals rather than pure drugs opens a pathway for the development of a phytomedicine derived from extracts of Hieronymiella spp.

The petroleum ether extract of Baccharis darwinii showed activity against Cryptococcus neoformans and dermatophytes. Bioactivity-guided fractionation of Baccharis darwinii has resulted in the isolation of three coumarins: 5’-hydroxy aurapten (anisocoumarin H, 1), aurapten (7-geranyloxycoumarin, 2) and 5’-oxoaurapten (diversinin, 3). The structures of these compounds were characterized by spectroscopic methods. These compounds were evaluated for their antimicrobialactivity against a panel of each, bacteria and fungi. Compound 3 showed the best activities against Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes with MICs = 15.6 µg/mL, followed by compound 1 whose MICs against the same fungi were 62.5 µg/mL. In addition they showed fungicidal rather than fungistatic activity. Both compounds showed moderate activity (MICs = 125 µg/mL) against Cryptococcus neoformans. This is the first report of the presence of compound 1 in B. darwinii.

The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC₅₀ = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.

Extracts from the Argentinean herb Tagetes mendocina Phil. (Asteraceae) were tested for antimicrobial activity against fungi, bacteria and protozoa. The different extracts (PE, DCM, MeOH and EtOAc) and the essential oil displayed activity mainly against dermatophytes, a group of fungi that produces skin infections. The bioassay-guided fractionation of PE, DCM and EtOAc extracts led to the isolation of eight compounds including two thiophenes, two acetophenone derivatives, dihydrorosefuran and three flavonoids. ITie thiophenes 5-(4-hydroxy- l-butynyl)-2,2'-bithienyl (BBTOH) (1) and its acetate (BBTOAc) (2) proved to be highly active against the dermatophytes Microsporum gypseum, Trichophyton rubrum and T. mentagrophytes with MIC values of 3.12, 3.12 and 6.25 µg/mL for compound 1 and 25, 3.12 and 6.25 µg/mLfor compound 2, respectively. In turn, the essential oil displayed a weak to modérate antifungal effect against M. gypseum with MIC = 250 µg/mL. ITie essential oil was examined by GC and GC-MS and 21 constituents (97.3%) were identified. (E) p-ocimene, (Z)-tagetone, (ii)-tagetone, (Z)-ocimenone, á-pinene and (E)-ocimenone were the major components. In addition, thiophenes 1 and 2 and 2-hydroxyacetophenone 3 showed antiprotozoal activity against Leishmania amazonensis, L. brasiliensis andi. infantum promastigotes with 100% lysis at 100 µg/mL.