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Article

Neuroprotective and Antioxidant Activity of Newly Synthesized N-Pyrrolyl Hydrazide-Hydrazones in Experimental Models of Neurotoxicity In Vitro and In Vivo

by
Martin Manov
1,*,
Denitsa Stefanova
1,
Magdalena Kondeva-Burdina
1,
Yordan Yordanov
1,
Martin Sharkov
2,
Diana Tzankova
2,
Emilio Mateev
2,
Maya Georgieva
2,
Georgi Popov
3,
Vasil Manov
3,
Maria Frosini
4,
Massimo Valoti
4 and
Virginia Tzankova
1,*
1
Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Pharmacy, Medical University—Sofia, 1000 Sofia, Bulgaria
2
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University—Sofia, 1000 Sofia, Bulgaria
3
Department of Internal Non-Communicable Diseases, Pathology and Pharmacology, Faculty of Veterinary Medicine, University of Forestry, 1111 Sofia, Bulgaria
4
Department of Life Sciences, University of Siena, 53100 Siena, Italy
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2026, 27(1), 370; https://doi.org/10.3390/ijms27010370 (registering DOI)
Submission received: 21 November 2025 / Revised: 16 December 2025 / Accepted: 26 December 2025 / Published: 29 December 2025
(This article belongs to the Section Molecular Neurobiology)
Versions Notes

Abstract

Oxidative stress plays a central role in the pathogenesis of neurodegenerative disorders, including Parkinson’s disease. Therefore, compounds with antioxidant and neuroprotective properties represent promising candidates for therapeutic development. N-pyrrolyl hydrazide-hydrazones, a class of pyrrole-based derivatives, have shown promising potential due to their diverse biological activities, including monoamine oxidase-B (MAO-B) inhibition. This study investigated the neuroprotective properties of 10 N-pyrrolyl hydrazide-hydrazones using experimental in vitro and in vivo models of neurodegeneration. The compounds were tested on SH-SY5Y neuroblastoma cells subjected to oxidative stress induced by 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP+). A battery of in vitro and in vivo experimental methods was used, including cell viability assay, reactive oxygen species (ROS) production, and apoptosis evaluation by quantifying the sub-G0/G1 cell population. In vivo neuroprotective efficacy was further tested in a rotenone-induced Parkinsonism mouse model by analyzing oxidative biomarkers and brain histopathology. Compounds 2, 4, 5, 6, and 10 significantly preserved cell viability in the 6-OHDA-induced toxicity model, while no protection was observed in the MPP+ model. Particularly compound 2 reduced ROS levels and apoptosis in SH-SY5Y cells. In vivo, compound 2 demonstrated strong antioxidant activity by maintaining glutathione levels and reducing lipid peroxidation. Histological analysis confirmed its protective effect against rotenone-induced neuronal damage. These results suggest that N-pyrrolyl hydrazide-hydrazones, especially compound 2, possess significant antioxidant and MAO-B inhibitory properties, supporting their potential as neuroprotective agents.
Keywords: N-pyrrolyl hydrazide-hydrazones; SH-SY5Y cells; 6-OHDA; MPP+ model; oxidative stress; rotenone-induced toxicity N-pyrrolyl hydrazide-hydrazones; SH-SY5Y cells; 6-OHDA; MPP+ model; oxidative stress; rotenone-induced toxicity

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MDPI and ACS Style

Manov, M.; Stefanova, D.; Kondeva-Burdina, M.; Yordanov, Y.; Sharkov, M.; Tzankova, D.; Mateev, E.; Georgieva, M.; Popov, G.; Manov, V.; et al. Neuroprotective and Antioxidant Activity of Newly Synthesized N-Pyrrolyl Hydrazide-Hydrazones in Experimental Models of Neurotoxicity In Vitro and In Vivo. Int. J. Mol. Sci. 2026, 27, 370. https://doi.org/10.3390/ijms27010370

AMA Style

Manov M, Stefanova D, Kondeva-Burdina M, Yordanov Y, Sharkov M, Tzankova D, Mateev E, Georgieva M, Popov G, Manov V, et al. Neuroprotective and Antioxidant Activity of Newly Synthesized N-Pyrrolyl Hydrazide-Hydrazones in Experimental Models of Neurotoxicity In Vitro and In Vivo. International Journal of Molecular Sciences. 2026; 27(1):370. https://doi.org/10.3390/ijms27010370

Chicago/Turabian Style

Manov, Martin, Denitsa Stefanova, Magdalena Kondeva-Burdina, Yordan Yordanov, Martin Sharkov, Diana Tzankova, Emilio Mateev, Maya Georgieva, Georgi Popov, Vasil Manov, and et al. 2026. "Neuroprotective and Antioxidant Activity of Newly Synthesized N-Pyrrolyl Hydrazide-Hydrazones in Experimental Models of Neurotoxicity In Vitro and In Vivo" International Journal of Molecular Sciences 27, no. 1: 370. https://doi.org/10.3390/ijms27010370

APA Style

Manov, M., Stefanova, D., Kondeva-Burdina, M., Yordanov, Y., Sharkov, M., Tzankova, D., Mateev, E., Georgieva, M., Popov, G., Manov, V., Frosini, M., Valoti, M., & Tzankova, V. (2026). Neuroprotective and Antioxidant Activity of Newly Synthesized N-Pyrrolyl Hydrazide-Hydrazones in Experimental Models of Neurotoxicity In Vitro and In Vivo. International Journal of Molecular Sciences, 27(1), 370. https://doi.org/10.3390/ijms27010370

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