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Turkish Journal of Chemistry

Author ORCID Identifier

EZGİ PEHLİVANLAR: 0000-0002-4088-7721

DENİZ ARCA ÇAKIR: 0000-0002-6110-1775

SONIA SANAJOU: 0000-0002-6751-5266

HÜLYA TEZEL YALÇIN: 0000-0002-1843-3424

TERKEN BAYDAR: 0000-0002-5497-9600

PINAR ERKEKOĞLU: 0000-0003-4713-7672

HANİFE AVCI: 0000-0002-1405-9754

RAHİME ŞİMŞEK: 0000-0002-8467-6336

DOI

10.55730/1300-0527.3686

Abstract

Inflammation is a response to injury and infection in the organism. It can be categorized as acute and chronic inflammation. Chronic inflammation is the underlying cause of many diseases such as Alzheimer's, diabetes, rheumatoid arthritis, atherosclerosis and cardiovascular diseases. Recent studies have proven the anti-inflammatory properties of 1,4-dihydropyridines (1,4-DHPs) and its derivatives, which have many biological properties including calcium channel blockers. The structures of the synthesized compounds were elucidated by IR, 1H-NMR, 13C-NMR and HRMS methods. The cytotoxic properties of the compounds were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in 3T3 cell line. Among the 15 compounds, the three compounds with the lowest cytotoxic properties were selected for further experiments. Inflammation was induced by lipooxygenase (LPS) and the effects of the selected compounds on the levels of reactive oxygen species (ROS), cytokines, complement C3 and C9 regulatory proteins were investigated. It was found that three selected compounds decreased the transforming growth factor beta 1 (TGF-b1) levels. Among these compounds, compound 3e provided the most significant decrease in this cytokine. Moreover, compound 3e increased both C3 and C9 levels. Molecular modeling studies also showed that compound 3e has a better affinity for TGF-b1. When the binding modes of these compounds in the active site of TGF-b1were analyzed, it was found that compound 3e had hydrophobic interactions with amino acids Leu142, Tyr84, and Ile13; halogen bond interactions with Asp92 and hydrogen bond interactions with amino acids Ser89, Gly88, and Gly14 in the active binding site. Further in vitro and in vivo studies are needed to show the possible mechanism of action of compound 3e.

Keywords

1, 4-DHP, hexahydroquinoline, cytotoxicity, ROS, inflammation, inflammatory cytokines, molecular docking

First Page

659

Last Page

675

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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