Drug Discovery, Organic Chemistry, Spectroscopy, Multidisciplinary
84
Scopus Publications
1812
Scholar Citations
24
Scholar h-index
43
Scholar i10-index
Scopus Publications
Mechanistic Exploration of N,N′-Disubstituted Diamines as Promising Chagas Disease Treatments Alejandro I. Recio-Balsells, Chantal Reigada, María Gabriela Mediavilla, Esteban Panozzo-Zénere, Miguel Villarreal Parra, et al. Pharmaceuticals, 2026 Introduction: Chagas disease, caused by the protozoan Trypanosoma cruzi, remains a major public health concern due to the limited effectiveness of current treatments, especially in the chronic stage. Objective: Here, we wanted to advance a library of 30 N,N′-disubstituted diamines as promising antichagasic agents and gain insight into the mechanism of action. Methods: The library was evaluated for activity against the T. cruzi amastigote stage and trypanocidal efficacy. In addition, selected compounds were tested as potential polyamine transport inhibitors, and a fluorescent analog was employed to investigate compound internalization. Results: Five compounds exhibited potent activity (pIC50 > 6.0), particularly those with short aliphatic linkers (3–6 carbon atoms), suggesting a structure–activity relationship favouring shorter chains. Mechanistic studies showed that compound 3c strongly inhibited polyamine transport, a vital pathway in T. cruzi, though this was not a universal mechanism among active hits, indicating the potential for multiple targets. A fluorescent analog confirmed intracellular uptake in amastigotes but lacked antiparasitic activity, likely due to disrupted pharmacophoric features. Importantly, none of the compounds demonstrated trypanocidal activity in long-term assays, and some showed cytotoxicity, particularly in the benzyloxy-substituted series. Conclusions: These findings position N,N′-disubstituted diamines as a viable scaffold for Chagas disease drug discovery. However, further optimization is required to enhance selectivity, achieve trypanocidal effects, and better understand the underlying mechanisms of action.
Progress and Prospects of Triazoles in Advanced Therapies for Parasitic Diseases Jaime A. Isern, Renzo Carlucci, Guillermo R. Labadie, Exequiel O. J. Porta Tropical Medicine and Infectious Disease, 2025 Parasitic diseases represent a severe global burden, with current treatments often limited by toxicity, drug resistance, and suboptimal efficacy in chronic infections. This review examines the emerging role of triazole-based compounds, originally developed as antifungals, in advanced antiparasitic therapy. Their unique structural properties, particularly those of 1,2,3- and 1,2,4-triazole isomers, facilitate diverse binding interactions and favorable pharmacokinetics. By leveraging innovative synthetic approaches, such as click chemistry (copper-catalyzed azide–alkyne cycloaddition) and structure-based design, researchers have repurposed and optimized triazole scaffolds to target essential parasite pathways, including sterol biosynthesis via CYP51 and other novel enzymatic routes. Preclinical studies in models of Chagas disease, leishmaniasis, malaria, and helminth infections demonstrate that derivatives like posaconazole, ravuconazole, and DSM265 exhibit potent in vitro and in vivo activity, although their primarily static effects have limited their success as monotherapies in chronic cases. Combination strategies and hybrid molecules have demonstrated the potential to enhance efficacy and mitigate drug resistance. Despite challenges in achieving complete parasite clearance and managing potential toxicity, interdisciplinary efforts across medicinal chemistry, parasitology, and clinical research highlight the significant potential of triazoles as components of next-generation, patient-friendly antiparasitic regimens. These findings support the further optimization and clinical evaluation of triazole-based agents to improve treatments for neglected parasitic diseases.
Repurposing antiparasitic N,N′-aliphatic diamine derivatives as promising antimycobacterial agents Alejandro I. Recio‐Balsells, Renzo Carlucci, Simone Giovannuzzi, Fabrizio Carta, Claudiu T. Supuran, et al. Archiv Der Pharmazie, 2024 In previous studies, we demonstrated the potent activity of a library of 25 N,N′‐disubstituted diamines (NNDDA) toward Trypanosomatid and Apicomplexa parasites. Considering the structure similarity between this collection and SQ109, an antituberculosis compound, and its compelling antiparasitic properties, we aimed to repurpose this library for tuberculosis treatment. We assayed this collection against Mycobacterium tuberculosis H37Rv and M. avium, obtaining several compounds with MIC values below 10 µM. The most active analogs were also evaluated against M. smegmatis, a non‐pathogenic species, and the non‐tuberculosis mycobacteria M. abscessus, M. kansasii, and M. fortuitum. 3c stands out as the lead mycobacterial compound of the collection, with potent activity against M. tuberculosis (minimal inhibitory concentration [MIC] = 3.4 µM) and moderate activity against M. smegmatis, M. kansasii, and M. fortuitum (all with MIC values of 26.8 µM). To unravel the mechanism of action, we employed the web‐based platform Polypharmacology Browser 2 (PPB2), obtaining carbonic anhydrases as potential drug targets. Nevertheless, none of the compounds displayed experimental inhibition. In summary, our study confirms the validity of the repurposing approach and underscores the antimycobacterial potential of NNDDA compounds, especially the analog 3c, setting a stepping stone for further studies.
Editorial: Combatting tropical diseases: a multi-level approach Santanu Sasidharan, Guillermo R. Labadie Frontiers in Cellular and Infection Microbiology, 2024 Topic to highlight the latest advances in the fi ght against tropical diseases. The Research Topic includes three articles on the prevention of viral diseases: dengue and hepatitis B. The review by Norshidah et al., focuses on the development of antivirals targeting the NS2B/NS3 protease of the dengue virus by examining 105 studies from 2015-2022 in depth. The review discusses the need to integrate in silico and in vitro screening for better antivirals against dengue virus. The second dengue article by Qin et al., shows the antiviral activity of Brucea javanica extracts and demonstrates that the oil emulsion is able to suppress hepatitis B virus replication by effectively upregulating IL-6 production. Interestingly, bruceine B, a major component of B. javanica seeds, was identi fi ed as the active agent responsible for IL-6 induction and hepatitis B virus inhibition. Bourgeois et al. in their study on dengue virus, evaluated kinase regulation using a machine learning approach that uses drug target information and a small drug screening to predict
1,2,3-Triazoles in Biomolecular Crystallography: A Geometrical Data-Mining Approach Renzo Carlucci, María-Natalia Lisa, Guillermo R. Labadie Journal of Medicinal Chemistry, 2023 The 1,2,3-triazole scaffold has become very attractive to identify new chemical entities in drug discovery projects. Despite the widespread use of click chemistry to synthesize numerous 123Ts, there are few drugs on the market that incorporate this scaffold as a substructure. To investigate the true potential of 123Ts in protein-ligand interactions, we examined the noncovalent interactions between the 1,2,3-triazole ring and amino acids in protein-ligand cocrystals using a geometrical approach. For this purpose, we constructed a nonredundant database of 220 PDB IDs from available 123T-protein cocrystal structures. Subsequently, using the Protein Ligand Interaction Profiler web platform (PLIP), we determined whether 1,2,3-triazoles primarily act as linkers or if they can be considered interactive scaffolds. We then manually analyzed the geometrical descriptors from 333 interactions between 1,4-disubstituted 123T rings and amino acid residues in proteins. This study demonstrates that 1,2,3-triazoles exhibit diverse preferred interactions with amino acids, which contribute to protein-ligand binding.
Chemobiosynthesis of new antimalarial macrolides Christopher D. Goodman, Mariana Useglio, Salvador Peirú, Guillermo R. Labadie, Geoffrey I. McFadden, et al. Antimicrobial Agents and Chemotherapy, 2013
Total synthesis of epothilone B Muralikrishna Valluri, Rama M. Hindupur, Panicker Bijoy, Guillermo Labadie, Jae-Chul Jung, et al. Organic Letters, 2001
Second-Generation N, N´-Disubstituted Aliphatic Diamines: Discovery of Potent Hits for Multi-Species Leishmaniasis Treatment. AI Recio-Balsells, EA Panozzo-Zenere, EM Coser, BA Ferreira, ... 2026
Mechanistic Exploration of N , N′ -Disubstituted Diamines as Promising Chagas Disease Treatments AI Recio-Balsells, C Reigada, MG Mediavilla, E Panozzo-Zénere, ... Pharmaceuticals 19 (1), 119 , 2026 2026 Citations: 1
XXIV Simposio Nacional de Química Orgánica (XXIV SINAQO)‐Special Collection NS Medrán, MJ Riveira, A La‐Venia, GR Labadie European Journal of Organic Chemistry 28 (38), e202500796 , 2025 2025
Advancing N, N′-disubstituted diamines in antimalarial drug development: Structure-activity relationships and mechanistic studies AI Recio-Balsells, E Panozzo-Zénere, R Carlucci, N Chaurasia, A Manhas, ... European Journal of Medicinal Chemistry 291, 117630 , 2025 2025 Citations: 1
Progress and prospects of triazoles in advanced therapies for parasitic diseases JA Isern, R Carlucci, GR Labadie, EOJ Porta Tropical Medicine and Infectious Disease 10 (5), 142 , 2025 2025 Citations: 10
Combatting tropical diseases: a multi-level approach S Sasidharan, GR Labadie Frontiers in Cellular and Infection Microbiology 14, 1406964 , 2024 2024
Repurposing antiparasitic N, N'-aliphatic diamine derivatives as promising antimycobacterial agents AI Recio-Balsells, R Carlucci, S Giovannuzzi, F Carta, CT Supuran, ... Archiv der Pharmazie, e2400597 , 2024 2024
Trypanocidal activity of liposomal isotretinoin and loratadine formulations C Reigada, F Digirolamo, F Galceran, M Saye, C Carrillo, P Torres, ... Journal of Drug Delivery Science and Technology 91, 105241 , 2024 2024 Citations: 4
Environmentally Friendly Process for Phytosterols Recovery from Residues of Biodiesel Production R Carlucci, JA Arancibia, GR Labadie Sustainable Chemistry and Pharmacy 37 (February 2024), 101360 , 2023 2023 Citations: 4
1, 2, 3-Triazoles in biomolecular crystallography: A geometrical Data-Mining approach R Carlucci, MN Lisa, GR Labadie Journal of Medicinal Chemistry 66 (21), 14377-14390 , 2023 2023 Citations: 13
Lipophilic modification of salirasib modulates the antiproliferative and antimigratory activity MS Ballari, EOJ Porta, EA Zalazar, CMB Etichetti, JM Padrón, JE Girardini, ... Bioorganic & Medicinal Chemistry 92, 117417 , 2023 2023 Citations: 4
Understanding the Fate of the Banert Cascade of Propargylic Azides: Sigmatropic versus Prototropic Pathway MMV Miguel Villarreal-Parra, Gabriel E. Di Gresia, Guillermo R. Labadie Journal of Organic Chemistry 88 (14), 9750–9759 , 2023 2023 Citations: 3
Garbage in, garbage out: How reliable training data improved a virtual screening approach against SARS-CoV-2 MPro MA Comini, S Ruatta, DN Prada Gori, M Fló Díaz, F Lorenzelli, ... Frontiers in Pharmacology 14, 1193282 , 2023 2023 Citations: 17
Systematic study of 1, 2, 3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases EOJ Porta, MS Ballari, R Carlucci, S Wilkinson, G Ma, BL Tekwani, ... European Journal of Medicinal Chemistry 254, 115378 , 2023 2023 Citations: 8
Expanding the scope of novel 1, 2, 3-triazole derivatives as new antiparasitic drug candidates R Carlucci, G Di Gresia, MG Mediavilla, JA Cricco, BL Tekwani, SI Khan, ... RSC Medicinal Chemistry 14 (1), 122-134 , 2023 2023 Citations: 17
Steryl glucosides recovered from biodiesel tank deposits are an excellent source of phytosterols R Carlucci, SN Jäger, GR Labadie Industrial Crops and Products 187, 115307 , 2022 2022 Citations: 7
Expanding the scope of prenylated 1, 2, 3-triazoles as new antiparasitic drug candidates R Carlucci, G Di Gresia, B Tekwani, S Khan, G Labadie ChemRxiv 2021 (1125) , 2021 2021 Citations: 1
Lipophilic Salirasib analogs with enhanced antiproliferative activity against human solid tumor cell lines [preprint] EOJ Porta, MS Ballari, JM Padrón, GR Labadie ChemRxiv , 2021 2021
Proline transport inhibitors trigger differential responses in Trypanosoma cruzi growth inhibition MS Ballari, L Fargnoli, L Pagura, J Cricco, A Silber, G Labadie ChemRxiv 2021 (0906) , 2021 2021 Citations: 1
Synthesis and interaction of terminal unsaturated chemical probes with Mycobacterium tuberculosis CYP124A1 L Diaz-Storani, AA Clary, DM Moreno, MS Ballari, EOJ Porta, ABJ Bracca, ... Bioorganic & Medicinal Chemistry 44, 116304 , 2021 2021
MOST CITED SCHOLAR PUBLICATIONS
Regio-and chemoselective covalent immobilization of proteins through unnatural amino acids C Gauchet, GR Labadie, CD Poulter Journal of the American Chemical Society 128 (29), 9274-9275 , 2006 2006 Citations: 187
Identification of a bifunctional maize C-and O-glucosyltransferase MLF Ferreyra, E Rodriguez, MI Casas, G Labadie, E Grotewold, P Casati Journal of Biological Chemistry 288 (44), 31678-31688 , 2013 2013 Citations: 151
Farnesyl diphosphate analogues with ω-bioorthogonal azide and alkyne functional groups for protein farnesyl transferase-catalyzed ligation reactions GR Labadie, R Viswanathan, CD Poulter The Journal of organic chemistry 72 (24), 9291-9297 , 2007 2007 Citations: 86
Tautomerism of representative aromatic α-hydroxy carbaldehyde anils as studied by spectroscopic methods and AM1 calculations. Synthesis of 10-hydroxyphenanthrene-9-carbaldehyde SH Alarcón, AC Olivieri, GR Labadie, RM Cravero, M González-Sierra Tetrahedron 51 (16), 4619-4626 , 1995 1995 Citations: 71
Identification of novel chemical scaffolds inhibiting trypanothione synthetase from pathogenic trypanosomatids D Benítez, A Medeiros, L Fiestas, EA Panozzo-Zenere, F Maiwald, ... PLoS neglected tropical diseases 10 (4), e0004617 , 2016 2016 Citations: 70
Total synthesis of epothilone B M Valluri, RM Hindupur, P Bijoy, G Labadie, JC Jung, MA Avery Organic letters 3 (23), 3607-3609 , 2001 2001 Citations: 64
Targeting tuberculosis through a small focused library of 1, 2, 3-triazoles GR Labadie, A de la Iglesia, HR Morbidoni Molecular diversity 15 (4), 1017-1024 , 2011 2011 Citations: 61
Endocannabinoids in Caenorhabditis elegans are essential for the mobilization of cholesterol from internal reserves C Galles, GM Prez, S Penkov, S Boland, EOJ Porta, SG Altabe, ... Scientific reports 8 (1), 6398 , 2018 2018 Citations: 58
Interaction of divalent metal ions withd-gluconic acid in the solid phase and aqueous solution GM Escandar, JMS Peregrin, MG Sierra, M Santoro, AA Frutos, SI Garci, ... Polyhedron 15 (13), 2251-2261 , 1996 1996 Citations: 58
Diamine derivatives with antiparasitic activities GR Labadie, SR Choi, MA Avery Bioorganic & medicinal chemistry letters 14 (3), 615-619 , 2004 2004 Citations: 54
Click chemistry decoration of amino sterols as promising strategy to developed new leishmanicidal drugs EOJ Porta, PB Carvalho, MA Avery, BL Tekwani, GR Labadie Steroids 79, 28-36 , 2014 2014 Citations: 44
Semisynthetic studies on the manzamine alkaloids KAE Sayed, AA Khalil, M Yousaf, G Labadie, GM Kumar, SG Franzblau, ... Journal of natural products 71 (3), 300-308 , 2008 2008 Citations: 38
Antitubercular activity of 1, 2, 3-triazolyl fatty acid derivatives DG Ghiano, A de la Iglesia, N Liu, PJ Tonge, HR Morbidoni, GR Labadie European journal of medicinal chemistry 125, 842-852 , 2017 2017 Citations: 37
Biochemical characterization of the minimal domains of an iterative eukaryotic polyketide synthase M Sabatini, S Comba, S Altabe, AI Recio‐Balsells, GR Labadie, E Takano, ... The FEBS Journal 285 (23), 4494-4511 , 2018 2018 Citations: 36
New one-pot synthesis of anti-tuberculosis compounds inspired on isoniazid DG Ghiano, A Recio-Balsells, A Bortolotti, LA Defelipe, A Turjanski, ... European journal of medicinal chemistry 208, 112699 , 2020 2020 Citations: 35
Computational approaches for drug discovery against trypanosomatid caused diseases CA Pereira, M Sayé, C Reigada, AM Silber, GR Labadie, MR Miranda, ... Parasitology, 1-68 , 2020 2020 Citations: 35
Antifungal activity and cytotoxicity of extracts and triterpenoid saponins obtained from the aerial parts of Anagallis arvensis L. JR Soberón, MA Sgariglia, AC Pastoriza, EM Soruco, SN Jäger, ... Journal of ethnopharmacology 203, 233-240 , 2017 2017 Citations: 34
Synthesis and antikinetoplastid activity of a series of N, N′-substituted diamines AP Caminos, EA Panozzo-Zenere, SR Wilkinson, BL Tekwani, ... Bioorganic & medicinal chemistry letters 22 (4), 1712-1715 , 2012 2012 Citations: 32
Chemobiosynthesis of new antimalarial macrolides CD Goodman, M Useglio, S Peirú, GR Labadie, GI McFadden, ... Antimicrobial agents and chemotherapy 57 (2), 907-913 , 2013 2013 Citations: 28
Interaction of zinc (II) ion withd-aldonic acids in the crystalline solid and aqueous solution GM Escandar, MG Sierra, JMS Peregrin, G Labadie, M Santoro, A Frutos, ... Polyhedron 13 (6-7), 909-914 , 1994 1994 Citations: 28
