Ionizing radiation‑induced modification of nialamide as an anti‑inflammatory agent against lipopolysaccharide‑induced RAW 264.7 and DH82 cells

Lee,Hanui; Jeong,Gyeong Han; Woo,So-Yeun; Choi,Hyo Jin; Chung,Byung Yeoup; Lee,Kyung-Bon; Bai,Hyoung-Woo

doi:10.3892/etm.2024.12480

Ionizing radiation‑induced modification of nialamide as an anti‑inflammatory agent against lipopolysaccharide‑induced RAW 264.7 and DH82 cells

Authors:
- Hanui Lee
- Gyeong Han Jeong
- So-Yeun Woo
- Hyo Jin Choi
- Byung Yeoup Chung
- Kyung-Bon Lee
- Hyoung-Woo Bai
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Affiliations: Research Division for Biotechnology, Advanced Radiation Technology Institute (ARTI), Korea Atomic Energy Research Institute (KAERI), Jeongeup, Jeollabuk 56212, Republic of Korea, Medical Device Development Center, Daegu‑Gyeongbuk Medical Innovation Foundation (K‑MEDI Hub), Daegu 41061, Republic of Korea, Department of Biology Education, Chonnam National University, Gwangju 61186, Republic of Korea
Published online on: March 11, 2024 https://doi.org/10.3892/etm.2024.12480
Article Number: 192
Copyright: © Lee et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Nialamide is a non‑selective monoamine oxidase inhibitor that was widely used as an antidepressant. However, it has been prohibited for decades in the depressive medicine market due to the adverse hepatotoxic side effects. The re‑use of drugs that have been withdrawn from the market represents a promising approach for the development of novel incrementally modified drugs and, in this context, ionizing radiation can serve as a powerful tool for producing new drug candidates. The present study exposed nialamide to γ radiation at 50 kGy to obtain the novel cyclized benzylamide, nialaminosin (compound 2), along with five known compounds, 3‑amino‑N‑benzylpropanamide (compound 3), 3‑methoxy‑N‑benzylpropanamide (compound 4), 3‑hydroxy‑N‑benzylpropanamide (HBPA; compound 5), N‑benzylpropanamide (compound 6) and isonicotinamide (compound 7). Among the isolated compounds, HBPA was established to inhibit the lipopolysaccharide‑induced overproduction of pro‑inflammatory mediators, including nitric oxide (NO) and prostaglandin E2 and cytokines including TNF‑α, IL‑6 and IL‑10, without causing cytotoxicity to both RAW 264.7 and DH82 cells. Furthermore, HBPA was found to reduce the protein expression of inducible NO synthase and cyclooxygenase‑2 in macrophages and compared with nialamide, it was established to have more potent radical scavenging activity. The present study therefore suggested the application of HBPA for the improvement of anti‑inflammatory properties using ionizing radiation technology on the withdrawn drug nialamide.

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