Martin Krähenbühl Amstalden

@usp.br

Department of Clinical Analyses, Toxicology and Food Science
School of Pharmaceutical Sciences of Ribeirão Preto

Martin Krähenbühl Amstalden


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https://researchid.co/mkamstalden

EDUCATION

(2013-2017) Bachelor in Pharmacy-Biochemistry: FCFRP-USP
(2018-) Masters in Biosciences and Biotechnology

RESEARCH INTERESTS

Glicobiology, Immunology and Biochemistry. Galectins, bacteria.
8

Scopus Publications

147

Scholar Citations

7

Scholar h-index

6

Scholar i10-index

Scopus Publications

  • Pre-trained molecular representations enable antimicrobial discovery
    Roberto Olayo-Alarcon, Martin K. Amstalden, Annamaria Zannoni, Medina Bajramovic, Cynthia M. Sharma, et al.
    Nature Communications, 2025
    The rise in antimicrobial resistance poses a worldwide threat, reducing the efficacy of common antibiotics. Determining the antimicrobial activity of new chemical compounds through experimental methods remains time-consuming and costly. While compound-centric deep learning models promise to accelerate this search and prioritization process, current strategies require large amounts of custom training data. Here, we introduce a lightweight computational strategy for antimicrobial discovery that builds on MolE (Molecular representation through redundancy reduced Embedding), a self-supervised deep learning framework that leverages unlabeled chemical structures to learn task-independent molecular representations. By combining MolE representation learning with available, experimentally validated compound-bacteria activity data, we design a general predictive model that enables assessing compounds with respect to their antimicrobial potential. Our model correctly identifies recent growth-inhibitory compounds that are structurally distinct from current antibiotics. Using this approach, we discover de novo, and experimentally confirm, three human-targeted drugs as growth inhibitors of Staphylococcus aureus. This framework offers a viable, cost-effective strategy to accelerate antibiotic discovery.
  • The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics
    Susanne Brenzinger, Martina Airoldi, Adewale Joseph Ogunleye, Karl Jugovic, Martin Krähenbühl Amstalden, et al.
    Nature Microbiology, 2024
  • Effects of C-Terminal-Ethyl-Esterification in a Snake-Venom-Based Peptide Against the Neurotoxicity of Acrolein in PC12 Cells
    Carolina P. Bernardes, Neife A. G. Santos, Tassia R. Costa, Danilo L. Menaldo, Flavia M. Sisti, et al.
    International Journal of Peptide Research and Therapeutics, 2023
  • Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion
    Carlos A. Fuzo, Ronaldo B. Martins, Thais F. C. Fraga‐Silva, Martin K. Amstalden, Thais Canassa De Leo, et al.
    Drug Development Research, 2022
    The global emergence of coronavirus disease 2019 (COVID-19) has caused substantial human casualties. Clinical manifestations of this disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and hyperinflammation. In face of the urgent demand for effective drugs to treat COVID-19, we have searched for candidate compounds using in silico approach followed by experimental validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F, as one of the best compounds out of 39 drug candidates. Celastrol reverted the gene expression signature from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells and irreversibly inhibited the recombinant forms of the viral and human cysteine proteases involved in virus invasion, such as Mpro (main protease), PLpro (papain-like protease), and recombinant human cathepsin L. Celastrol suppressed SARS-CoV-2 replication in human and monkey cell lines and decreased interleukin-6 (IL-6) secretion in the SARS-CoV-2-infected human cell line. Celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity, and inhibited in vitro replication of the parental and SARS-CoV-2 variant. Therefore, celastrol is a promising lead compound to develop new drug candidates to face COVID-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells.
  • MG-Pe: A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine
    Stellee M. P. Biscaia, Cassiano Pires, Francislaine A. R. Lívero, Daniel L. Bellan, Israel Bini, et al.
    International Journal of Molecular Sciences, 2022
    Melanoma is a highly metastatic and rapidly progressing cancer, a leading cause of mortality among skin cancers. The melanoma microenvironment, formed from the activity of malignant cells on the extracellular matrix and the recruitment of immune cells, plays an active role in the development of drug resistance and tumor recurrence, which are clinical challenges in cancer treatment. These tumoral metabolic processes are affected by proteins, including Galectin-3 (Gal-3), which is extensively involved in cancer development. Previously, we characterized a partially methylated mannogalactan (MG-Pe) with antimelanoma activities. In vivo models of melanoma were used to observe MG-Pe effects in survival, spontaneous, and experimental metastases and in tissue oxidative stress. Analytical assays for the molecular interaction of MG-Pe and Gal-3 were performed using a quartz crystal microbalance, atomic force microscopy, and contact angle tensiometer. MG-Pe exhibits an additive effect when administered together with the chemotherapeutic agent dacarbazine, leading to increased survival of treated mice, metastases reduction, and the modulation of oxidative stress. MG-Pe binds to galectin-3. Furthermore, MG-Pe antitumor effects were substantially reduced in Gal-3/KO mice. Our results showed that the novel Gal-3 ligand, MG-Pe, has both antitumor and antimetastatic effects, alone or in combination with chemotherapy.
  • Ruthenium (II) complex cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6-hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective cytotoxicity
    Mônica Soares Costa, Yasmim Garcia Gonçalves, Bruna Cristina Borges, Marcelo José Barbosa Silva, Martin Krähenbühl Amstalden, et al.
    Scientific Reports, 2020
    Ruthenium complexes have been extensively explored as potential molecules for cancer treatment. Considering our previous findings on the remarkable cytotoxic activity exhibited by the ruthenium (II) complex 3-hydroxy-4-methoxybenzoate (hmxbato)-cis-[RuII(ŋ2-O2CC7H7O2)(dppm)2]PF6 against Leishmania promastigotes and also the similar metabolic characteristics between trypanosomatids and tumor cells, the present study aimed to analyze the anticancer potential of hmxbato against lung tumor cells, as well as the partial death mechanisms involved. Hmxbato demonstrated selective cytotoxicity against A549 lung tumor cells. In addition, this complex at a concentration of 3.8 µM was able to expressively increase the generation of reactive oxygen species (ROS) in tumor cells, causing an oxidative stress that may culminate in: (1) reduction in cellular proliferation; (2) changes in cell morphology and organization patterns of the actin cytoskeleton; (3) cell arrest in the G2/M phase of the cell cycle; (4) apoptosis; (5) changes in the mitochondrial membrane potential and (6) initial DNA damage. Furthermore, we demonstrated that the induction of programmed cell death can occur by the intrinsic apoptotic pathway through the activation of caspases. It is also worth highlighting that hmxbato exhibited predominant actions on A549 tumor cells in comparison to BEAS-2B normal bronchial epithelium cells, which makes this complex an interesting candidate for the design of new drugs against lung cancer.
  • A Synthetic Snake-Venom-Based Tripeptide Protects PC12 Cells from the Neurotoxicity of Acrolein by Improving Axonal Plasticity and Bioenergetics
    Carolina P. Bernardes, Neife A. G. Santos, Tassia R. Costa, Flavia Sisti, Lilian Amaral, et al.
    Neurotoxicity Research, 2020
    The synthetic peptide p-BTX-I is based on the native peptide (formed by glutamic acid, valine and tryptophan) isolated from Bothrops atrox venom. We have previously demonstrated its neuroprotective and neurotrophic properties in PC12 cells treated with the dopaminergic neurotoxin 1-methyl-4-phenylpyridinium (MPP+). Now, we have investigated the neuroprotective effects and mechanisms of p-BTX-I against the toxicity of acrolein in PC12 cells. Studies have demonstrated that acrolein might play an important role in the etiology of Alzheimer’s disease (AD), which is characterized by neuronal and synaptic loss. Our results showed that not only acrolein reduced cell differentiation and cell viability, but also altered the expression of markers of synaptic communication (synapsin I), energy metabolism (AMPK-α, Sirt I and glucose uptake), and cytoskeleton (β-III-tubulin). Treatment with p-BTX-I increased the percentage of differentiation in cells treated with acrolein and significantly attenuated cell viability loss, besides counteracting the negative effects of acrolein on synapsin I, AMPK-α, Sirt I, glucose uptake, and β-III-tubulin. Additionally, p-BTX-I alone increased the expression of apolipoprotein E (apoE) gene, associated with the proteolytic degradation of β-amyloid peptide aggregates, a hallmark of AD. Taken together, these findings demonstrate that p-BTX-I protects against acrolein-induced neurotoxicity and might be a tool for the development of novel drugs for the treatment of neurodegenerative diseases.
  • CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress
    Tássia R. Costa, Martin K. Amstalden, Diego L. Ribeiro, Danilo L. Menaldo, Marco A. Sartim, et al.
    Toxicology, 2018
    Snake venom L-amino acid oxidases (SV-LAAOs) are enzymes of great interest in research due to their many biological effects with therapeutic potential. CR-LAAO, an L-amino acid oxidase from Calloselasma rhodostoma snake venom, is a well described SV-LAAO with immunomodulatory, antiparasitic, microbicidal, and antitumor effects. In this study, we evaluated the genotoxic potential of this enzyme in human peripheral blood mononuclear cells (PBMC) and HepG2 tumor cells, as well as its interaction with these cells, its impact on the expression of DNA repair and antioxidant pathway genes, and reactive oxygen species (ROS)-induced intracellular production. Flow cytometry analysis of FITC-labelled CR-LAAO showed higher specificity of interaction with HepG2 cells than PBMC. Moreover, CR-LAAO significantly increased intracellular levels of ROS only in HepG2 tumor cells, as assessed by fluorescence. CR-LAAO also induced genotoxicity in HepG2 cells and PBMC after 4 h of stimulus, with DNA damages persisting in HepG2 cells after 24 h. To investigate the molecular basis underlying the genotoxicity attributed to CR-LAAO, we analyzed the expression profile (mRNA levels) of 44 genes involved in DNA repair and antioxidant pathways in HepG2 cells by RT2 Profiler polymerase chain reaction array. CR-LAAO altered the tumor cell expression of DNA repair genes, with two downregulated (XRCC4 and TOPBP1) and three upregulated (ERCC6, RAD52 and CDKN1) genes. In addition, two genes of the antioxidant pathway were upregulated (GPX3 and MPO), probably in an attempt to protect tumor cells from oxidative damage. In conclusion, our data suggest that CR-LAAO possesses higher binding affinity to HepG2 tumor cells than to PBMC, its genotoxic mechanism is possibly caused by the oxidative stress related to the production of H2O2, and is also capable of modulating genes related to the DNA repair system and antioxidant pathways.

RECENT SCHOLAR PUBLICATIONS

  • Pre-trained molecular representations enable antimicrobial discovery
    R Olayo-Alarcon, MK Amstalden, A Zannoni, M Bajramovic, CM Sharma, ...
    Nature Communications 16 (1), 3420 , 2025
    2025
    Citations: 24
  • Statistical end-to-end analysis of large-scale microbial growth data with DGrowthR
    M Feldl, R Olayo-Alarcon, MK Amstalden, A Zannoni, S Peschel, ...
    bioRxiv, 2025.03. 25.645164 , 2025
    2025
    Citations: 6
  • The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics
    S Brenzinger, M Airoldi, AJ Ogunleye, K Jugovic, MK Amstalden, ...
    Nature Microbiology 9 (1), 251-262 , 2024
    2024
    Citations: 22
  • Effects of C-Terminal-Ethyl-Esterification in a Snake-Venom-Based Peptide Against the Neurotoxicity of Acrolein in PC12 Cells
    CP Bernardes, NAG Santos, TR Costa, DL Menaldo, FM Sisti, ...
    International Journal of Peptide Research and Therapeutics 29 (3), 41 , 2023
    2023
    Citations: 1
  • Celastrol: A lead compound that inhibits SARS‐CoV‐2 replication, the activity of viral and human cysteine proteases, and virus‐induced IL‐6 secretion
    CA Fuzo, RB Martins, TFC Fraga‐Silva, MK Amstalden, ...
    Drug Development Research 83 (7), 1623-1640 , 2022
    2022
    Citations: 16
  • MG- Pe : A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine
    SMP Biscaia, C Pires, FAR Lívero, DL Bellan, I Bini, SO Bustos, ...
    International journal of molecular sciences 23 (14), 7635 , 2022
    2022
    Citations: 9
  • Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation
    CA Fuzo, RB Martins, TFC Fraga-Silva, MK Amstalden, TC De Leo, ...
    bioRxiv, 2021.04. 20.439992 , 2021
    2021
    Citations: 4
  • Ruthenium (II) complex cis -[Ru II (ŋ 2 -O 2 CC 7 H 7 O 2 )(dppm) 2 ]PF 6 -hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective …
    MS Costa, YG Goncalves, BC Borges, MJB Silva, MK Amstalden, ...
    Scientific Reports 10 (1), 15410 , 2020
    2020
    Citations: 33
  • A synthetic snake-venom-based tripeptide protects PC12 cells from the neurotoxicity of acrolein by improving axonal plasticity and bioenergetics
    CP Bernardes, NAG Santos, TR Costa, F Sisti, L Amaral, DL Menaldo, ...
    Neurotoxicity Research 37 (1), 227-237 , 2020
    2020
    Citations: 13
  • CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress
    TR Costa, MK Amstalden, DL Ribeiro, DL Menaldo, MA Sartim, AF Aissa, ...
    Toxicology 404, 42-48 , 2018
    2018
    Citations: 19

MOST CITED SCHOLAR PUBLICATIONS

  • Ruthenium (II) complex cis -[Ru II (ŋ 2 -O 2 CC 7 H 7 O 2 )(dppm) 2 ]PF 6 -hmxbato induces ROS-mediated apoptosis in lung tumor cells producing selective …
    MS Costa, YG Goncalves, BC Borges, MJB Silva, MK Amstalden, ...
    Scientific Reports 10 (1), 15410 , 2020
    2020
    Citations: 33
  • Pre-trained molecular representations enable antimicrobial discovery
    R Olayo-Alarcon, MK Amstalden, A Zannoni, M Bajramovic, CM Sharma, ...
    Nature Communications 16 (1), 3420 , 2025
    2025
    Citations: 24
  • The Vibrio cholerae CBASS phage defence system modulates resistance and killing by antifolate antibiotics
    S Brenzinger, M Airoldi, AJ Ogunleye, K Jugovic, MK Amstalden, ...
    Nature Microbiology 9 (1), 251-262 , 2024
    2024
    Citations: 22
  • CR-LAAO causes genotoxic damage in HepG2 tumor cells by oxidative stress
    TR Costa, MK Amstalden, DL Ribeiro, DL Menaldo, MA Sartim, AF Aissa, ...
    Toxicology 404, 42-48 , 2018
    2018
    Citations: 19
  • Celastrol: A lead compound that inhibits SARS‐CoV‐2 replication, the activity of viral and human cysteine proteases, and virus‐induced IL‐6 secretion
    CA Fuzo, RB Martins, TFC Fraga‐Silva, MK Amstalden, ...
    Drug Development Research 83 (7), 1623-1640 , 2022
    2022
    Citations: 16
  • A synthetic snake-venom-based tripeptide protects PC12 cells from the neurotoxicity of acrolein by improving axonal plasticity and bioenergetics
    CP Bernardes, NAG Santos, TR Costa, F Sisti, L Amaral, DL Menaldo, ...
    Neurotoxicity Research 37 (1), 227-237 , 2020
    2020
    Citations: 13
  • MG- Pe : A Novel Galectin-3 Ligand with Antimelanoma Properties and Adjuvant Effects to Dacarbazine
    SMP Biscaia, C Pires, FAR Lívero, DL Bellan, I Bini, SO Bustos, ...
    International journal of molecular sciences 23 (14), 7635 , 2022
    2022
    Citations: 9
  • Statistical end-to-end analysis of large-scale microbial growth data with DGrowthR
    M Feldl, R Olayo-Alarcon, MK Amstalden, A Zannoni, S Peschel, ...
    bioRxiv, 2025.03. 25.645164 , 2025
    2025
    Citations: 6
  • Drug repurposing to face Covid-19: Celastrol, a potential leading drug capable of inhibiting SARS-CoV-2 replication and induced inflammation
    CA Fuzo, RB Martins, TFC Fraga-Silva, MK Amstalden, TC De Leo, ...
    bioRxiv, 2021.04. 20.439992 , 2021
    2021
    Citations: 4
  • Effects of C-Terminal-Ethyl-Esterification in a Snake-Venom-Based Peptide Against the Neurotoxicity of Acrolein in PC12 Cells
    CP Bernardes, NAG Santos, TR Costa, DL Menaldo, FM Sisti, ...
    International Journal of Peptide Research and Therapeutics 29 (3), 41 , 2023
    2023
    Citations: 1