http://hdl.handle.net/10366/151253 2026-04-22T22:16:35Z http://hdl.handle.net/10366/169325 Fermented foods have been used for several years all over the world, due to their unique nutritional characteristics and because fermentation promotes conservation and food security. Moreover, fermented foods and beverages have a strong impact on human gut microbiota. Papaya is the fruit of the Carica papaya plant, traditionally used as a medicinal fruit, but there are also references to the use of the fermented form of this fruit. The main purpose of this review is to provide an improved understanding of fermented papaya nutritional and health applications. A literature search was conducted in the PubMed and Google Scholar databases. Both in vitro and in vivo studies were included. According to the retrieved studies, fermented papaya has proven to be an excellent antioxidant and an excellent nutraceutical adjuvant in combined therapies against several diseases, such as Alzheimer’s disease, allergic reactions, anticancer activity, and anemias. Therefore, it is concluded that fermented papaya has many benefits for human health and can be used as prevention or aid in the treatment of various diseases. 2022-02-16T00:00:00Z http://hdl.handle.net/10366/169083 Background The genus Cytinus, recognised as one of the most enigmatic in the plant kingdom, has garnered attention for its bioactive potential, particularly its skin anti-ageing properties. Despite this recognition, much remains to be accomplished regarding deciphering and isolating its most active compounds. Hypothesis This study aimed to identify the compounds responsible for C. hypocistis skin anti-ageing potential. Methods Using multivariate analysis, a biochemometric approach was applied to identify the discriminant metabolites by integrating extracts' chemical profile (Liquid Chromatography–High-Resolution Mass Spectrometry, LCsingle bondHRMS) and bioactive properties. The identified bioactive metabolite was structurally elucidated by 1D and 2D Nuclear Magnetic Resonance (NMR). Results Among the studied bioactivities, the anti-elastase results exhibited a significant variation among the samples from different years. After the biochemometric analysis, the compound 2,3:4,6-bis(hexahydroxydiphenoyl)glucose, with a molecular mass of 784.075 Da, was structurally elucidated as the discriminant feature responsible for the outstanding human neutrophil elastase inhibition. Remarkably, the subfraction containing this compound exhibited a tenfold improvement in neutrophil elastase inhibition efficacy compared to the crude extract; its effectiveness fell within the same range as SPCK, a potent irreversible neutrophil elastase inhibitor. Moreover, this subfraction displayed no cytotoxicity or phototoxicity and excellent efficacy for the tested anti-ageing properties. Conclusions Hydrolysable tannins were confirmed as the metabolites behind C. hypocistis skin anti-ageing properties, effectively mitigating critical molecular mechanisms that influence the phenotypically distinct ageing clinical manifestations. Pedunculagin was particularly effective in inhibiting neutrophil elastase, considered one of the most destructive enzymes in skin ageing. 2024-07-01T00:00:00Z http://hdl.handle.net/10366/169081 Tannins are a class of phenolic compounds commonly found in plants and studied for their bioactive and inhibitory enzyme properties. Cytinus hypocistis (L.) L. is a wild edible parasitic plant whose biological properties have been correlated with its high tannin content. Thus, studying the extraction of tannins from C. hypocistis will give comprehensive clues to enhance the recovery of these high added-value bioactive compounds. The present work applied Response Surface Methodology (RSM) to optimise tannins extraction using Heat-Assisted (HAE) and Ultrasound-Assisted (UAE) methods. Two three-factor Rotatable Central Composite Designs were used to assess the linear, quadratic, and interaction effects of the independent variables on the target responses. The obtained results from both extraction systems revealed high ethanol percentages as the critical factor in increasing tannin content. The optimum global processing conditions predicted by the polynomial models were 95.1 min, 46.4 °C, and 74.3% ethanol for HAE; and 18.7 min, 327.4 W, and 69.3% ethanol for UAE. Following these conditions, 200 mg and 178 mg of total tannins per g of extract were recovered using HAE and UAE, correspondingly. Although HAE presented a higher final response, the UAE stood out as a time-saving technique. 2021-12-01T00:00:00Z http://hdl.handle.net/10366/169079 Cytinus hypocistis whole plant and its three different parts (petals, stalks, and nectar) were chemically characterised and their biological properties evaluated. A total of 17 phenolic compounds were identified, being galloyl-bis-HHDP-glucose the most abundant. All the tested extracts showed high antioxidant capacity, with the petals exhibiting the most promising results both in the OxHLIA (IC50 = 0.279 ng/mL) and TBARS (IC50 = 0.342 ng/mL) assays. For the antidiabetic and anti-tyrosinase enzyme inhibitory assays, the stalk extract presented the lowest IC50 values, 0.039 mg/mL and 0.09 mg/mL, respectively. Regarding antibacterial activity, all tested extracts displayed broad-spectrum microbial inhibition against both Gram-positive and Gram-negative bacteria. Similarly, all extracts displayed effective anti-proliferation activity against four tested tumour cell lines (NCI–H460, HeLa, HepG2, and MCF-7), with no toxicity observed for a non-tumour cell line. Considering the anti-inflammatory activity, the petals showed the highest nitric oxide inhibition (IC50 = 127 μg/mL). These results point C. hypocistis as a promising source of health-promoting biomolecules. 2020-02-01T00:00:00Z http://hdl.handle.net/10366/168864 Cytinus hypocistis (L.) L. is a comestible holoparasite with great potential for cosmeceutical application. Although its high tannin content has been associated with its bioactive and inhibitory enzyme properties, this is the first report establishing a relationship between parasite and host (Halimium lasianthum (Lam.) Greuter) phenolic profile and bioactive properties. Thus, five extracts (aerial and root extracts of non-parasited and parasited H. lasianthum and C. hypocistis) were evaluated. The tentative identification of both species comprises 39 phenolic compounds. Hydrolysable tannins and flavonoids were the main identified groups in C. hypocistis and H. lasianthum extracts, respectively. Regarding bioactivities, C. hypocistis exhibited excellent antioxidant results both in Oxidative Haemolysis (OxHLIA) and inhibition of Thiobarbituric Acid Reactive Substances Formation (TBARS). The tested extracts presented antimicrobial inhibition, anti-inflammatory activity, and effective cytotoxicity against tumour cells. C. hypocistis exhibited the lowest cytotoxicity on a non-tumour cell line. Principal Component Analysis (PCA) was a suitable approach to analyse differences among samples, explaining up to 67% of data variability and suggesting no similarities between parasite and host phenolic composition and bioactivities. Therefore, this comparative study emphasises the significance of both species as a source of biologically active compounds. 2022-02-01T00:00:00Z http://hdl.handle.net/10366/168760 Ethnopharmacological relevance: Medicinal plants are rich in bioactive compounds with diverse properties that can preserve human health. Eryngium bourgatii is used in traditional medicine to purify the blood. Species of this genus have been used for their antibacterial, antitumor, antifungal or antiparasitic properties among others. Aim of the study: In this work, the antiparasitic properties against Leishmania donovani, Trypanosoma cruzi, and Plasmodium falciparum were evaluated. Materials and methods: Methyl tert-butyl ether (MTBE), dichloromethane (DCM), and ethyl acetate (EtOAc) extracts of the roots and the non-flowering aerial parts were obtained by maceration at room temperature. Some of them were partitioned with solvents of increasing polarity, specifically n-hexane (n-Hex), dichloromethane (DCM), and ethyl acetate (EA) to isolate different fractions. Growth inhibition assays were performed against the three protozoa (L. donovani, T. cruzi, and P. falciparum). The active fractions were subsequently separated by chromatography to determine the secondary metabolites responsible for the activity. In addition, GC-MS studies were performed to further analyse the composition of the extracts and fractions. Results: Regarding the roots, the MTBE extract was the most potent leishmanicidal (77.7 % inhibition at 10 μg/ mL). The activity increased in its n-Hex fraction (95.3 % inhibition), and in the DCM fraction, both leishmanicidal (93.6 %) and anti-Chagas activity (92.2 %) improved. Furanone 12, a new natural compound, was the main component of the extract and the most potent leishmanicide (96.7 %), sixteen times less than the reference drug, Amphotericin B. 11-Acetoxyfalcarindiol (19) was the most potent anti-Chagas (89.1 % inhibition). Regarding the aerial parts, the DCM extract was the most potent leishmanicide (83.3 %), which improved in its DCM fraction (95.7 %), mainly attributed to compound 12. The DCM fraction of the MTBE extract produced the best antichagasic result (93.3 % inhibition), attributed to falcarindiol (17). Practically, the same compounds were identified in the roots as in the aerial parts, but in different proportions. Nine pure compounds were isolated; 34 were identified in roots and 37 in the aerial parts by GC-MS, with alkyne compounds leading, followed by sesquiterpenes and fatty acids. 2025-04-19T00:00:00Z http://hdl.handle.net/10366/168759 Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson’s Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to μM. The most potent compound with IC50 = 0.6 nM was the 3′,4′-dichloro-BPH 16, which showed highly selective and reversible MAO-B inhibitory activity. Furthermore, the most selective BPHs displayed a significant protection against the apoptosis, and mitochondrial toxic effects induced by 6-hydroxydopamine (6OHDA) on SH-SY5Y cells, used as a cellular model of PD. The results of virtual binding studies on the most potent compounds docked in MAO-B and MAO-A were in agreement with the potencies and selectivity indexes found experimentally. Additionally, related to toxicity risks, drug-likeness and ADME properties, the predictions found for the most relevant BPHs in this research were within those ranges established for drug candidates. 2024-03-03T00:00:00Z http://hdl.handle.net/10366/168756 Tuberculosis remains a major public health problem and one of the top ten causes of death worldwide. The alarming increase in multidrug-resistant and extensively resistant variants (MDR, pre-XDR, and XDR) makes the disease more difficult to treat and control. New drugs that act against MDR/XDR strains are needed for programs to contain this major epidemic. The present study aimed to evaluate new compounds related to dihydro-sphingosine and ethambutol against sensitive and pre-XDR Mycobacterium strains, as well as to characterize the pharmacological activity through in vitro and in silico approaches in mmpL3 protein. Of the 48 compounds analyzed, 11 demonstrated good to moderate activity on sensitive and MDR Mycobacterium tuberculosis (Mtb), with a Minimum Inhibitory Concentration (MIC) ranging from 1.5 to 8 μM. They presented 2 to 14 times greater potency of activity when compared to ethambutol in pre-XDR strain, and demonstrated a selectivity index varying between 2.21 and 82.17. The substance 12b when combined with rifampicin, showed a synergistic effect (FICI = 0.5) on sensitive and MDR Mtb. It has also been shown to have a concentration-dependent intracellular bactericidal effect, and a time-dependent bactericidal effect in M. smegmatis and pre-XDR M. tuberculosis. The binding mode of the compounds in its cavity was identified through molecular docking and using a predicted structural model of mmpL3. Finally, we observed by transmission electron microscopy the induction of damage to the cell wall integrity of M. tuberculosis treated with the substance 12b. With these findings, we demonstrate the potential of a 2-aminoalkanol derivative to be a prototype substance and candidate for further optimization of molecular structure and anti-tubercular activity in preclinical studies. 2023-10-05T00:00:00Z http://hdl.handle.net/10366/168755 The deficit of effective treatments for Chagas disease has led to searching for new substances with therapeutic potential. Natural products possess a wide variety of chemical structural motifs and are thus a valuable source of diverse lead compounds for the development of new drugs. Castanedia santamartensis is endemic to Colombia, and local indigenous communities often use it to treat skin sores from leishmaniasis; however, its mechanism of action against the infective form of Trypanosoma cruzi has not been determined. Thus, we performed chemical and biological studies of two alcoholic leaf extracts of C. santamartensis to identify their active fractions and relate them to a trypanocidal effect and evaluate their mechanism of action. Alcoholic extracts were obtained through cold maceration at room temperature and fractionated using classical column chromatography. Both ethanolic and methanolic extracts displayed activity against T. cruzi. Chemical studies revealed that kaurenoic acid was the major component of one fraction of the methanolic extract and two fractions of the ethanolic extract of C. santamartensis leaves. Moreover, caryophyllene oxide, kaurenol, taraxasterol acetate, pentadecanone, and methyl and ethyl esters of palmitate, as well as a group of phenolic compounds, including ferulic acid, caffeic acid, chlorogenic acid, myricetin, quercitrin, and cryptochlorogenic acid were identified in the most active fractions. Kaurenoic acid and the most active fractions CS400 and CS402 collapsed the mitochondrial membrane potential in trypomastigotes, demonstrating for the first time the likely mechanism against T. cruzi, probably due to interactions with other components of the fractions. 2022-04-15T00:00:00Z http://hdl.handle.net/10366/168744 Gastrointestinal nematode infections are the main diseases in herds of small ruminants. Resistance to the main established drugs has become a worldwide problem. The purpose of this study is to obtain and evaluate the in vitro ovicidal and larvicidal activity of some 2-phenylbenzimidazole derivatives on susceptible and resistant strains of Teladorsagia circumcincta. Compounds were prepared by known procedures from substituted o-phenylenediamines and arylaldehydes or intermediate sodium 1-hydroxyphenylmethanesulfonate derivatives. Egg Hatch Test (EHT), Larval Mortality Test (LMT) and Larval Migration Inhibition Test (LMIT) were used in the initial screening of compounds at 50 μM concentration, and EC50 values were determined for the most potent compounds. Cytotoxicity evaluation of compounds was conducted on human Caco-2 and HepG2 cell lines to calculate their Selectivity Indexes (SI). At 50 μM concentration, nine out of twenty-four compounds displayed more than 98% ovicidal activity on a susceptible strain, and four of them showed more than 86% on one resistant strain. The most potent ovicidal benzimidazole (BZ) 3 showed EC50 = 6.30 μM, for the susceptible strain, while BZ 2 showed the lowest EC50 value of 14.5 μM for the resistant strain. Docking studies of most potent compounds in a modelled Teladorsagia tubulin indicated an inverted orientation for BZ 1 in the colchicine binding site, probably due to its fair interaction with glutamic acid at codon 198, which could justify its inactivity against the resistant strain of T. circumcincta. 2020-12-15T00:00:00Z http://hdl.handle.net/10366/168231 Introduction: Drug development has traditionally used mathematical models to predict formulation behavior. Objective: Building artificial neural networks for the drug release evaluation of drug delivery systems using sustained-release metronidazole-coated colonic hydrophilic matrices as a model. Methods: The technological factors associated with the biopharmaceutical performance of hydrophilic metronidazole matrices were evaluated using a quality by design approach (QbD). The developed neural network includes variables related to the technological process for producing the matrices. These are related to the materials used, such as the type and viscosity of core polymers, the type of coating agent, or the matrix production process, such as the mixing time of core materials or the percentage of the coating agent. The output variables of the neural network were the percentages of drug released in vitro at 1, 6, 12, and 24 h and the mean dissolution time of the matrix. An iterative quasi-Newton method was used to train the artificial neural network. Results: A neural network with excellent prediction capacity allows selecting the technological variables with the greatest influence on the % of drug dissolved: the type of coating agent used and the percentage of the total weight increase after coating for 1 h and 6 h of drug release and also the viscosity of the HPMC for 12 and 24 h. Conclusions: The optimized neural network demonstrated an excellent predictive capacity for in vitro drug dissolution profiles, allowing the use of this type of methodology based on artificial intelligence methods in the optimization of drug delivery systems. 2025-11-10T00:00:00Z http://hdl.handle.net/10366/166972 Natural products are the ideal basis for the design of novel efficient molecular entities. Podophyllotoxin, a naturally occurring cyclolignan, is an example of natural product which displays a high versatility from a biological activity point of view. Based on its unique chemical structure, different derivatives have been synthesized presenting the original antitumoral properties associated with the compound, i.e., the tubulin polymerization inhibition and arising anti-topoisomerase II activity from structural modifications on the cyclolignan skeleton. In this report, we present a novel conjugate or hybrid which chemically combines both biological activities in one single molecule. Chemical design has been planned based in our lead compound, podophyllic aldehyde, as an inhibitor of tubulin polymerization, and in etoposide, an approved antitumoral drug targeting topoisomerase II. The cytotoxicity and selectivity of the novel synthetized hybrid has been evaluated in several cell lines of different solid tumors. In addition, these dual functional effects of the novel compound have been also evaluated by molecular docking approaches. 2020-01-01T00:00:00Z http://hdl.handle.net/10366/166971 Podophyllotoxin is a naturally occurring cyclolignan isolated from rhizomes of Podophyllum sp. In the clinic, it is used mainly as an antiviral; however, its antitumor activity is even more interesting. While podophyllotoxin possesses severe side effects that limit its development as an anticancer agent, nevertheless, it has become a good lead compound for the synthesis of derivatives with fewer side effects and better selectivity. Several examples, such as etoposide, highlight the potential of this natural product for chemomodulation in the search for new antitumor agents. This review focuses on the recent chemical modifications (2017–mid-2023) of the podophyllotoxin skeleton performed mainly at the C-ring (but also at the lactone D-ring and at the trimethoxyphenyl E-ring) together with their biological properties. Special emphasis is placed on hybrids or conjugates with other natural products (either primary or secondary metabolites) and other molecules (heterocycles, benzoheterocycles, synthetic drugs, and other moieties) that contribute to improved podophyllotoxin bioactivity. In fact, hybridization has been a good strategy to design podophyllotoxin derivatives with enhanced bioactivity. The way in which the two components are joined (directly or through spacers) was also considered for the organization of this review. This comprehensive perspective is presented with the aim of guiding the medicinal chemistry community in the design of new podophyllotoxin-based drugs with improved anticancer properties. 2023-01-01T00:00:00Z http://hdl.handle.net/10366/166970 Quinolines have been an interest of study for a few decades due to the importance of this system in natural and pharmaceutical products. Since their discovery in the nineteenth century, many medicinal properties have been found for quinoline compounds. Firstly, as an anti-parasitic agent against malaria and then against many other diseases, such as, other parasitic infections, HIV, bacterial infections and cancer. Consequently, many synthetic methods have been developed to afford the quinoline ring. In this review we look back at traditional methods and look forward to the most recent and promising “green” methods for the synthesis of quinolines. Also, we review the newest advances in therapeutic compounds based on the quinoline skeleton for the treatment of parasitic and cancer diseases and the most recent applications of quinoline derivatives in drug delivery systems. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/166969 Podophyllotoxin is a natural compound belonging to the lignan family and is well-known for its great antitumor activity. However, it shows several limitations, such as severe side effects and some pharmacokinetics problems, including low water solubility, which hinders its application as an anticancer agent. Over the past few years, antitumor research has been focused on developing nanotechnology-based medicines or nanomedicines which allow researchers to improve the pharmacokinetic properties of anticancer compounds. Following this trend, podophyllotoxin nanoconjugates have been obtained to overcome its biopharmaceutical drawbacks and to enhance its antitumor properties. The objective of this review is to highlight the advances made over the past few years (2017–2023) regarding the inclusion of podophyllotoxin in different nanosystems. Among the huge variety of nanoconjugates of diverse nature, drug delivery systems bearing podophyllotoxin as cytotoxic payload are organic nanoparticles mainly based on polymer carriers, micelles, and liposomes. Along with the description of their pharmacological properties as antitumorals and the advantages compared to the free drug in terms of biocompatibility, solubility, and selectivity, we also provide insight into the synthetic procedures developed to obtain those podophyllotoxin-nanocarriers. Typical procedures in this regard are self-assembly techniques, nanoprecipitations, or ionic gelation methods among others. This comprehensive perspective aims to enlighten the medicinal chemistry community about the tendencies followed in the design of new podophyllotoxin-based drug delivery systems, their features and applications. 2025-01-01T00:00:00Z http://hdl.handle.net/10366/166968 When new antitumor therapy drugs are discovered, it is essential to address new target molecules from the point of view of chemical structure and to carry out efficient and systematic evaluation. In the case of natural products and derived compounds, it is of special importance to investigate chemomodulation to further explore antitumoral pharmacological activities. In this work, the compound podophyllic aldehyde, a cyclolignan derived from the chemomodulation of the natural product podophyllotoxin, has been evaluated for its viability, influence on the cell cycle, and effects on intracellular signaling. We used functional proteomics characterization for the evaluation. Compared with the FDA-approved drug etoposide (another podophyllotoxin derivative), we found interesting results regarding the cytotoxicity of podophyllic aldehyde. In addition, we were able to observe the effect of mitotic arrest in the treated cells. The use of podophyllic aldehyde resulted in increased cytotoxicity in solid tumor cell lines, compared to etoposide, and blocked the cycle more successfully than etoposide. High-throughput analysis of the deregulated proteins revealed a selective antimitotic mechanism of action of podophyllic aldehyde in the HT-29 cell line, in contrast with other solid and hematological tumor lines. Also, the apoptotic profile of podophyllic aldehyde was deciphered. The cell death mechanism is activated independently of the cell cycle profile. The results of these targeted analyses have also shown a significant response to the signaling of kinases, key proteins involved in signaling cascades for cell proliferation or metastasis. Thanks to this comprehensive analysis of podophyllic aldehyde, remarkable cytotoxic, antimitotic, and other antitumoral features have been discovered that will repurpose this compound for further chemical transformations and antitumoral analysis. 2024-01-01T00:00:00Z