Investigation of New Benzimidazole Derivative Compounds' Effects on A549 Cell Line


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Duran G. G. , Kucuk M. U. , Algul Ö., Terzi M. Y.

BRAZILIAN ARCHIVES OF BIOLOGY AND TECHNOLOGY, vol.63, 2020 (SCI-Expanded) identifier

  • Publication Type: Article / Article
  • Volume: 63
  • Publication Date: 2020
  • Doi Number: 10.1590/1678-4324-2020190364
  • Journal Name: BRAZILIAN ARCHIVES OF BIOLOGY AND TECHNOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Animal Behavior Abstracts, Aquatic Science & Fisheries Abstracts (ASFA), BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Veterinary Science Database, Directory of Open Access Journals
  • Keywords: A549, benzimidazole, inflammation, anti-inflammatory, NF-KAPPA-B, ANTIOXIDANT, EXPRESSION, MAPK, SCAFFOLD, ICAM-1, COX-2
  • Erzincan Binali Yildirim University Affiliated: No

Abstract

Chronic inflammation is a common indication of several diseases, e.g. asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, etc. Benzimidazole derivatives are preferable compounds to design new analgesic and anti-inflammatory substances due to their unique biological features. We aimed to investigate the effect of a newly synthesized benzimidazole derivative, ORT-83, on A549 human lung adenocarcinoma cell line. ORT-83 was synthesized, and a non-cytotoxic concentration of ORT-83 on A549 cells was detected with MTT assay. To analyze the anti-inflammatory effect of ORT-83, an inflammatory cell culture model was established by stimulating A549 cell line with IL1-beta (10 ng/ml). After 2 hours of treatment with IL1-beta to induce inflammation, A549 cells were exposed to ORT-83 (0.78 mu g/ml) for 24 hours. Thereafter gene expression analyses were performed with qRT-PCR. We found that ORT-83 significantly suppressed the gene expression levels of the proinflammatory cytokines; IL-6, NFkB, and TNF-alpha. However, the increased levels of IL-10 (2.8 folds) by IL-1 beta induction did not change after ORT-83 and/or dexamethasone (Dex: positive control) treatments. While Dex; a COX-2 inhibitor, reduced the COX-2 expression level in inflammatory cells from 10.03 folds to 0.71 folds, ORT-83 reduced its level to 4.37 folds. iNOS expression levels did not change in any experimental groups. In conclusion, we showed that ORT-83 exerted its anti-inflammatory effects by repressing the gene expression of proinflammatory cytokines in the inflammation-induced A549 cell line. Although ORT-83 had a weaker COX-2 inhibitory effect compared to Dex, it was shown to be still a strong anti-inflammatory compound.