In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives
Melanoma is the most aggressive and lethal type of skin cancer, responsible for approximately 60,000 deaths annually. The main strategy for treating melanoma is surgery to completely remove the lesion and its margins. However, for more advanced cases with a high recurrence rate, the preferred approa...
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Elsevier
2025-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580825000378 |
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| author | Héverton Mendes Araújo Gabriel Acácio de Moura Yasmim Mendes Rocha Cristian Vicson Pinheiro Gomes Valentina Nascimento e Melo de Oliveira Ronaldo Nascimento de Oliveira Larissa Deadame de Figueiredo Nicolete Emanuel Paula Magalhães Ramon R.P.P.B. de Menezes Roberto Nicolete |
| author_facet | Héverton Mendes Araújo Gabriel Acácio de Moura Yasmim Mendes Rocha Cristian Vicson Pinheiro Gomes Valentina Nascimento e Melo de Oliveira Ronaldo Nascimento de Oliveira Larissa Deadame de Figueiredo Nicolete Emanuel Paula Magalhães Ramon R.P.P.B. de Menezes Roberto Nicolete |
| author_sort | Héverton Mendes Araújo |
| collection | DOAJ |
| description | Melanoma is the most aggressive and lethal type of skin cancer, responsible for approximately 60,000 deaths annually. The main strategy for treating melanoma is surgery to completely remove the lesion and its margins. However, for more advanced cases with a high recurrence rate, the preferred approach is to combine chemotherapy with immunotherapy treatments. Tumor-associated macrophages (TAMs) are the most abundant leukocytes in solid tumors. Current immunotherapy approaches target TAMs by inhibiting pro-tumoral TAMs and activating anti-tumoral TAMs, repolarizing them to the M1 phenotype. The antitumor and immunomodulatory activities of molecules derived from 1,2,4-oxadiazole, as demonstrated in the literature, highlight the potential of this class as a source of promising candidates for therapeutic applications. Thus, the present study aims to evaluate the antitumor and immunomodulatory effects of the synthetic derivative 1,2,4-oxadiazole, N-cyclohexyl-3-(3-methylphenyl)-1,2,4-oxadiazole-5-amine (1,2,4-oxadiazole derivative 2), in melanoma cells and murine Bone Marrow-Derived Macrophages (BMDMs). Cytotoxicity in B16–F10 and BMDMs cells was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method. 1,2,4-oxadiazole derivative 2 exhibited antiproliferative effects on both cell lines, being 2.6 times more selective for B16–F10. Necrosis was identified as the active induced death pathway. BMDMs isolated and exposed to 1,2,4-oxadiazole derivative 2 polarize to the M1 phenotype and induce TNF-α at a concentration of 64.34 μM. Exposure to melanoma murine supernatants also promotes M1 polarization. Supernatants containing traces of 1,2,4-oxadiazole derivative 2 (Supernatants B, C, and D) increased the percentage of M1 cells compared to Supernatant A, as well as elevated levels of nitrite, TNF-α, and IL-12. 1,2,4-oxadiazole derivative 2 combined with Supernatant A and 1,2,4-oxadiazole derivative 2 combined with LPS also resulted in higher M1 polarization, suggesting a synergistic effect on M1 polarization and TNF-α production. Our findings underscore the significance of the 1,2,4-oxadiazole compound class and highlight the potential of 1,2,4-oxadiazole derivative 2 as an antitumoral and immunotherapeutic agent. |
| format | Article |
| id | doaj-art-09d7236b2e264b548306464c2db12dfc |
| institution | Kabale University |
| issn | 2405-5808 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
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| series | Biochemistry and Biophysics Reports |
| spelling | doaj-art-09d7236b2e264b548306464c2db12dfc2025-02-12T05:31:21ZengElsevierBiochemistry and Biophysics Reports2405-58082025-03-0141101950In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivativesHéverton Mendes Araújo0Gabriel Acácio de Moura1Yasmim Mendes Rocha2Cristian Vicson Pinheiro Gomes3Valentina Nascimento e Melo de Oliveira4Ronaldo Nascimento de Oliveira5Larissa Deadame de Figueiredo Nicolete6Emanuel Paula Magalhães7Ramon R.P.P.B. de Menezes8Roberto Nicolete9Post-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Fundação Oswaldo Cruz, Fiocruz, Fiocruz Ceará, Eusébio, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Fundação Oswaldo Cruz, Fiocruz, Fiocruz Ceará, Eusébio, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Fundação Oswaldo Cruz, Fiocruz, Fiocruz Ceará, Eusébio, CE, BrazilInstituto Federal de Educação Ciência e Tecnologia de Pernambuco, Campus Ipojuca, Ipojuca-PE, BrazilDepartment of Chemistry, Rural Federal University of Pernambuco, Recife-PE, BrazilHealth Sciences Institute, University of International Integration of the Afro-Brazilian Lusophony (UNILAB), Redenção, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, BrazilPost-Graduate Program in Pharmaceutical Sciences (PPGCF), Federal University of Ceará (UFC), Fortaleza, CE, Brazil; Fundação Oswaldo Cruz, Fiocruz, Fiocruz Ceará, Eusébio, CE, Brazil; Corresponding author. São José Street, S/N – Precabura, Zip Code: 61773-270, Eusébio – Ceará, Brazil.Melanoma is the most aggressive and lethal type of skin cancer, responsible for approximately 60,000 deaths annually. The main strategy for treating melanoma is surgery to completely remove the lesion and its margins. However, for more advanced cases with a high recurrence rate, the preferred approach is to combine chemotherapy with immunotherapy treatments. Tumor-associated macrophages (TAMs) are the most abundant leukocytes in solid tumors. Current immunotherapy approaches target TAMs by inhibiting pro-tumoral TAMs and activating anti-tumoral TAMs, repolarizing them to the M1 phenotype. The antitumor and immunomodulatory activities of molecules derived from 1,2,4-oxadiazole, as demonstrated in the literature, highlight the potential of this class as a source of promising candidates for therapeutic applications. Thus, the present study aims to evaluate the antitumor and immunomodulatory effects of the synthetic derivative 1,2,4-oxadiazole, N-cyclohexyl-3-(3-methylphenyl)-1,2,4-oxadiazole-5-amine (1,2,4-oxadiazole derivative 2), in melanoma cells and murine Bone Marrow-Derived Macrophages (BMDMs). Cytotoxicity in B16–F10 and BMDMs cells was assessed using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT method. 1,2,4-oxadiazole derivative 2 exhibited antiproliferative effects on both cell lines, being 2.6 times more selective for B16–F10. Necrosis was identified as the active induced death pathway. BMDMs isolated and exposed to 1,2,4-oxadiazole derivative 2 polarize to the M1 phenotype and induce TNF-α at a concentration of 64.34 μM. Exposure to melanoma murine supernatants also promotes M1 polarization. Supernatants containing traces of 1,2,4-oxadiazole derivative 2 (Supernatants B, C, and D) increased the percentage of M1 cells compared to Supernatant A, as well as elevated levels of nitrite, TNF-α, and IL-12. 1,2,4-oxadiazole derivative 2 combined with Supernatant A and 1,2,4-oxadiazole derivative 2 combined with LPS also resulted in higher M1 polarization, suggesting a synergistic effect on M1 polarization and TNF-α production. Our findings underscore the significance of the 1,2,4-oxadiazole compound class and highlight the potential of 1,2,4-oxadiazole derivative 2 as an antitumoral and immunotherapeutic agent.http://www.sciencedirect.com/science/article/pii/S24055808250003781,2,4 oxadiazoleMacrophagesPolarizationMurine melanomaImmunotherapy |
| spellingShingle | Héverton Mendes Araújo Gabriel Acácio de Moura Yasmim Mendes Rocha Cristian Vicson Pinheiro Gomes Valentina Nascimento e Melo de Oliveira Ronaldo Nascimento de Oliveira Larissa Deadame de Figueiredo Nicolete Emanuel Paula Magalhães Ramon R.P.P.B. de Menezes Roberto Nicolete In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives Biochemistry and Biophysics Reports 1,2,4 oxadiazole Macrophages Polarization Murine melanoma Immunotherapy |
| title | In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives |
| title_full | In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives |
| title_fullStr | In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives |
| title_full_unstemmed | In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives |
| title_short | In vitro antitumor and immunomodulatory activities of 1,2,4-oxadiazole derivatives |
| title_sort | in vitro antitumor and immunomodulatory activities of 1 2 4 oxadiazole derivatives |
| topic | 1,2,4 oxadiazole Macrophages Polarization Murine melanoma Immunotherapy |
| url | http://www.sciencedirect.com/science/article/pii/S2405580825000378 |
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