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  1. Article ; Online: Early Pharmacological Profiling of Antiproliferative Compounds by Live Cell Imaging.

    Puerta, Adrián / González-Bakker, Aday / Santos, Guido / Padrón, José M

    Molecules (Basel, Switzerland)

    2022  Volume 27, Issue 16

    Abstract: Natural products represent an excellent source of unprecedented anticancer compounds. However, the identification of the mechanism of action remains a major challenge. Several techniques and methodologies have been considered, but with limited success. ... ...

    Abstract Natural products represent an excellent source of unprecedented anticancer compounds. However, the identification of the mechanism of action remains a major challenge. Several techniques and methodologies have been considered, but with limited success. In this work, we explored the combination of live cell imaging and machine learning techniques as a promising tool to depict in a fast and affordable test the mode of action of natural compounds with antiproliferative activity. To develop the model, we selected the non-small cell lung cancer cell line SW1573, which was exposed to the known antimitotic drugs paclitaxel, colchicine and vinblastine. The novelty of our methodology focuses on two main features with the highest relevance, (a) meaningful phenotypic metrics, and (b) fast Fourier transform (FFT) of the time series of the phenotypic parameters into their corresponding amplitudes and phases. The resulting algorithm was able to cluster the microtubule disruptors, and meanwhile showed a negative correlation between paclitaxel and the other treatments. The FFT approach was able to group the samples as efficiently as checking by eye. This methodology could easily scale to group a large amount of data without visual supervision.
    MeSH term(s) Antimitotic Agents/pharmacology ; Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Humans ; Lung Neoplasms/metabolism ; Microtubules/metabolism ; Paclitaxel/metabolism ; Paclitaxel/pharmacology ; Tubulin/metabolism
    Chemical Substances Antimitotic Agents ; Antineoplastic Agents ; Tubulin ; Paclitaxel (P88XT4IS4D)
    Language English
    Publishing date 2022-08-17
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 1413402-0
    ISSN 1420-3049 ; 1431-5165 ; 1420-3049
    ISSN (online) 1420-3049
    ISSN 1431-5165 ; 1420-3049
    DOI 10.3390/molecules27165261
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Early pharmacological profiling of isatin derivatives as potent and selective cytotoxic agents.

    Puerta, Adrián / González-Bakker, Aday / Brandão, Pedro / Pineiro, Marta / Burke, Anthony J / Giovannetti, Elisa / Fernandes, Miguel X / Padrón, José M

    Biochemical pharmacology

    2024  Volume 222, Page(s) 116059

    Abstract: Isatin derivatives have attracted a lot of interest for their potential in the development of new anticancer drugs. A library of 38 isatin derivatives, created through an Ugi four-component reaction, underwent an initial screening in a panel of six human ...

    Abstract Isatin derivatives have attracted a lot of interest for their potential in the development of new anticancer drugs. A library of 38 isatin derivatives, created through an Ugi four-component reaction, underwent an initial screening in a panel of six human solid tumor cell lines. The four most active derivatives were then selected for further testing. These compounds showed selectivity towards the non-small cell lung cancer (NSCLC) cell line SW1573, whilst NSCLC A549 cells were barely affected. The combination of phenotypic assays, including wound healing, clonogenic and continuous live cell imaging provided a deeper understanding of the compounds' mode of action. In particular, the latter demonstrated that isatin derivatives were able to induce necroptosis in SW1573 cells. The kinetics of cell death showed that necroptosis appeared after 2.5 h of exposure, which could be delayed to 7 h when co-treated with necrostatin-1. Interaction between the isatin derivatives and the KRAS G12C protein variant was discarded after in silico studies. Further studies are warranted to identify the cellular target responsible for the observed selectivity among cell lines.
    MeSH term(s) Humans ; Cytotoxins ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Isatin/pharmacology ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Drug Screening Assays, Antitumor ; Structure-Activity Relationship ; Cell Proliferation ; Molecular Structure
    Chemical Substances Cytotoxins ; Antineoplastic Agents ; Isatin (82X95S7M06)
    Language English
    Publishing date 2024-02-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2024.116059
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Correction: One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity.

    Bosica, Giovanna / Demanuele, Kaylie / Padrón, José Manuel / Puerta, Adrián

    Beilstein journal of organic chemistry

    2021  Volume 17, Page(s) 2026–2027

    Abstract: This corrects the article DOI: 10.3762/bjoc.16.235.]. ...

    Abstract [This corrects the article DOI: 10.3762/bjoc.16.235.].
    Language English
    Publishing date 2021-08-10
    Publishing country Germany
    Document type Published Erratum
    ZDB-ID 2192461-2
    ISSN 1860-5397
    ISSN 1860-5397
    DOI 10.3762/bjoc.17.130
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Alkaloid Profiling, Anti-Enzymatic and Antiproliferative Activity of the Endemic Chilean Amaryllidaceae

    Fernández-Galleguillos, Carlos / Romero-Parra, Javier / Puerta, Adrián / Padrón, José M / Simirgiotis, Mario J

    Metabolites

    2022  Volume 12, Issue 2

    Abstract: This research aims to identify the alkaloid profile and to evaluate the enzyme inhibitory potential and antiproliferative effects of the Amaryllidaceae ... ...

    Abstract This research aims to identify the alkaloid profile and to evaluate the enzyme inhibitory potential and antiproliferative effects of the Amaryllidaceae plant
    Language English
    Publishing date 2022-02-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12020188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Antiproliferative effect of natural and semisynthetic polyethers from

    Santiago-Benítez, Adrián J / Puerta, Adrián / Padrón, José M / Norte, Manuel / Fernández, José J / Hernández Daranas, Antonio / Cen-Pacheco, Francisco

    Natural product research

    2023  , Page(s) 1–7

    Abstract: Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this ...

    Abstract Squalene-derived polyethers are a unique class of compounds that display a great diversity of structures and a broad array of bioactivities, among which its notable antiproliferative activity stands out against various types of cancer cell lines. In this study, eighteen triterpene squalene-derived polyethers, including twelve natural products and six synthetic derivatives, obtained from the red alga
    Language English
    Publishing date 2023-11-11
    Publishing country England
    Document type Journal Article
    ZDB-ID 2185747-7
    ISSN 1478-6427 ; 1478-6419
    ISSN (online) 1478-6427
    ISSN 1478-6419
    DOI 10.1080/14786419.2023.2280176
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Tetranuclear Ru

    Alguacil, Andrés / Scalambra, Franco / Lorenzo-Luis, Pablo / Puerta, Adrián / González-Bakker, Aday / Mendoza, Zenaida / Padrón, José M / Romerosa, Antonio

    Dalton transactions (Cambridge, England : 2003)

    2023  Volume 52, Issue 28, Page(s) 9541–9545

    Abstract: Complexes [{RuCp( ... ...

    Abstract Complexes [{RuCp(PPh
    MeSH term(s) Humans ; HeLa Cells ; DNA
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2023-07-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 1472887-4
    ISSN 1477-9234 ; 1364-5447 ; 0300-9246 ; 1477-9226
    ISSN (online) 1477-9234 ; 1364-5447
    ISSN 0300-9246 ; 1477-9226
    DOI 10.1039/d3dt01284k
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Coumarin-azasugar-benzyl conjugates as non-neurotoxic dual inhibitors of butyrylcholinesterase and cancer cell growth.

    Vaaland Holmgard, I Caroline / González-Bakker, Aday / Poeta, Eleonora / Puerta, Adrián / Fernandes, Miguel X / Monti, Barbara / Fernández-Bolaños, José G / Padrón, José M / López, Óscar / Lindbäck, Emil

    Organic & biomolecular chemistry

    2024  Volume 22, Issue 17, Page(s) 3425–3438

    Abstract: We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The ... ...

    Abstract We have applied the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction to prepare a library of ten coumarin-azasugar-benzyl conjugates and two phthalimide-azasugar-benzyl conjugates with potential anti-Alzheimer and anti-cancer properties. The compounds were evaluated as cholinesterase inhibitors, demonstrating a general preference, of up to 676-fold, for the inhibition of butyrylcholinesterase (BuChE) over acetylcholinesterase (AChE). Nine of the compounds behaved as stronger BuChE inhibitors than galantamine, one of the few drugs in clinical use against Alzheimer's disease. The most potent BuChE inhibitor (IC
    MeSH term(s) Coumarins/chemistry ; Coumarins/pharmacology ; Coumarins/chemical synthesis ; Butyrylcholinesterase/metabolism ; Humans ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/chemistry ; Cholinesterase Inhibitors/chemical synthesis ; Cell Proliferation/drug effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/chemical synthesis ; Animals ; Cell Line, Tumor ; Structure-Activity Relationship ; Molecular Structure ; Drug Screening Assays, Antitumor ; Aza Compounds/chemistry ; Aza Compounds/pharmacology ; Aza Compounds/chemical synthesis ; Dose-Response Relationship, Drug ; Neurons/drug effects
    Chemical Substances Coumarins ; Butyrylcholinesterase (EC 3.1.1.8) ; Cholinesterase Inhibitors ; Antineoplastic Agents ; coumarin (A4VZ22K1WT) ; Aza Compounds
    Language English
    Publishing date 2024-05-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d4ob00312h
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: One-pot multicomponent green Hantzsch synthesis of 1,2-dihydropyridine derivatives with antiproliferative activity.

    Bosica, Giovanna / Demanuele, Kaylie / Padrón, José M / Puerta, Adrián

    Beilstein journal of organic chemistry

    2020  Volume 16, Page(s) 2862–2869

    Abstract: A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various ... ...

    Abstract A rapid route for obtaining unsymmetrical 1,2-dihydropyridines (1,2-DHPs) as opposed to 1,4-dihydropyridines (1,4-DHPs) has been achieved via a one-pot multicomponent Hantzsch reaction. A benign protocol has been developed for the preparation of various 1,2-dihydropyridine derivatives using heterogenized phosphotungstic acid on alumina support (40 wt %). High yields of over 75% have been accomplished in just 2-3.5 h after screening several heterogeneous catalysts and investigating the optimal reaction conditions. The catalyst chosen has passed the heterogeneity test and was shown to have the potential of being reused for up to 8 consecutive cycles before having a significant loss in activity. In addition, aromatic aldehydes gave the aforementioned regioisomer while the classical 1,4-DHPs were obtained when carrying out the reaction using aliphatic aldehydes. The preliminary study of the antiproliferative activity against human solid tumor cells demonstrated that 1,2-DHPs could inhibit cancer cell growth in the low micromolar range.
    Language English
    Publishing date 2020-11-24
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2192461-2
    ISSN 1860-5397
    ISSN 1860-5397
    DOI 10.3762/bjoc.16.235
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Investigation of the enantioselectivity of acetylcholinesterase and butyrylcholinesterase upon inhibition by tacrine-iminosugar heterodimers.

    Vaaland, I Caroline / López, Óscar / Puerta, Adrián / Fernandes, Miguel X / Padrón, José M / Fernández-Bolaños, José G / Sydnes, Magne O / Lindbäck, Emil

    Journal of enzyme inhibition and medicinal chemistry

    2022  Volume 38, Issue 1, Page(s) 349–360

    Abstract: The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held ... ...

    Abstract The copper-catalysed azide-alkyne cycloaddition was applied to prepare three enantiomeric pairs of heterodimers containing a tacrine residue and a 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) or 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) moiety held together
    MeSH term(s) Humans ; Butyrylcholinesterase ; Acetylcholinesterase ; Tacrine/pharmacology ; Alkynes
    Chemical Substances Butyrylcholinesterase (EC 3.1.1.8) ; Acetylcholinesterase (EC 3.1.1.7) ; Tacrine (4VX7YNB537) ; arabitol (YFV05Y57M9) ; Alkynes
    Language English
    Publishing date 2022-09-30
    Publishing country England
    Document type Journal Article
    ZDB-ID 2082578-X
    ISSN 1475-6374 ; 1475-6366
    ISSN (online) 1475-6374
    ISSN 1475-6366
    DOI 10.1080/14756366.2022.2150762
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Phenolic Fingerprinting and Bioactivity Profiling of Extracts and Isolated Compounds from Gypothamnium pinifolium Phil

    Barrientos, Ruth E. / Ibáñez, Elena / Puerta, Adrián / Padrón, José M. / Paredes, Adrián / Cifuentes, Fredi / Romero-Parra, Javier / Palacios, Xabier / Bórquez, Jorge / Simirgiotis, Mario J.

    Antioxidants. 2022 Nov. 22, v. 11, no. 12

    2022  

    Abstract: Gypothamnium pinifolium Phil. (Asteraceae) is a small shrub that grows in the Paposo Valley of the II Antofagasta Region of Chile. This initial study is of the high-resolution phenolic fingerprinting, antioxidant activity, the relaxation effects in rat ... ...

    Abstract Gypothamnium pinifolium Phil. (Asteraceae) is a small shrub that grows in the Paposo Valley of the II Antofagasta Region of Chile. This initial study is of the high-resolution phenolic fingerprinting, antioxidant activity, the relaxation effects in rat aorta, the inhibitory enzyme potential, plus the antiproliferative activity of the ethyl acetate and n-hexane extract from G. pinifolium and its two major isolated secondary metabolites (one coumarin: 2-nor-1,2-secolycoserone, and one diterpene: ent-labda-8,13-E-diene-15-ol). The study involves using ultra-high-performance liquid chromatography todiode array detection coupled with Q-Orbitrap mass spectrometry analysis (UHPLC-PDA-Orbi-trap-MS), in which various compounds were identified, including specific coumarins. The n-hexane extract showed total phenolic and flavonoid contents of 517.4 ± 12.5 mg GAE/100 g extract and 72.3 ± 3.7 mg QE/100 g extract, respectively. In addition, the antioxidant activity of the n-hexane extract was assessed using in-vitro assays such as bleaching of DPPH and ABTS (IC₅₀: 14.3 ± 0.52 and 2.51 ± 0.43 µg extract/mL, respectively), FRAP (347.12 ± 1.15 μmol Trolox equivalent/g extract), and ORAC (287.3 ± 1.54 μmol Trolox equivalents/g extract). Furthermore, the inhibition against cholinesterases (acetylcholinesterase (AChE) 4.58 ± 0.04 µg/mL, butyrylcholinesterase (BChE) IC₅₀: 23.44 ± 0.03 µg/mL) and tyrosinase (IC₅₀: 9.25 ± 0.15 µg/mL) enzymes of the n-hexane extract, and main compounds (IC₅₀: 1.21 ± 0.03 µg/mL, 11.23 ± 0.02 µg/mL, 3.23 ± 0.12 µg/mL, and 103.43 ± 16.86 µg/mL, correspondingly for the most active coumarin 1) were measured. The antiproliferative potential of the extracts and the two principal compounds against several solid human cancer cells was investigated. All of them showed good activity against cancer cells. Label-free live-cell imaging studies on HeLa cells exposed to the isolated coumarin and the diterpene enabled the observation of cell death and several apoptotic hallmarks. Our results indicate that G. pinifolium Phil. is a valuable source of secondary metabolites with potential activity against noncommunicable diseases.
    Keywords Asteraceae ; acetylcholinesterase ; antioxidant activity ; aorta ; apoptosis ; cholinesterase ; coumarin ; diterpenoids ; ethyl acetate ; flavonoids ; hexane ; humans ; mass spectrometry ; rats ; secondary metabolites ; shrubs ; ultra-performance liquid chromatography ; Chile
    Language English
    Dates of publication 2022-1122
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2704216-9
    ISSN 2076-3921
    ISSN 2076-3921
    DOI 10.3390/antiox11122313
    Database NAL-Catalogue (AGRICOLA)

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