TY - JOUR
T1 - 1,4-disubstituted 1h-1,2,3-triazoles for renal diseases
T2 - Studies of viability, anti-inflammatory, and antioxidant activities
AU - Cheng, Ching Yi
AU - Haque, Ashanul
AU - Hsieh, Ming Fa
AU - Hassan, Syed Imran
AU - Faizi, Md Serajul Haque
AU - Dege, Necmi
AU - Khan, Muhammad S.
N1 - Funding Information:
Funding: This research was funded by Ministry of Science and Technology, Taiwan, grant number MOST 108-2119-M-033-002 and Chang Gung Medical Research Foundation, Taiwan under grant number CMRPF3G0013; CMRPF3K0041 and BMRPD16, Chang Gung University of Science and Technology, Taiwan under grant number ZRRPF3J0081.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Inflammation is a hallmark of many metabolic diseases. We previously showed that ferrocene-appended 1H-1,2,3-triazole hybrids inhibit nitric oxide (NO) production in in vitro models of lipopolysaccharide-induced inflammation in the BV-2 cell. In the present study, we explored the viability, anti-inflammatory, and antioxidant potential of ferrocene-1H-1,2,3-triazole hybrids using biochemical assays in rat mesangial cells (RMCs). We found that, among all the ferrocene-1H-1,2,3-triazole hybrids, X2–X4 exhibited an antioxidant effect on mitochondrial free radicals. Among all the studied compounds, X4 demonstrated the best anti-inflammatory effect on RMCs. These results were supplemented by in silico studies including molecular docking with human cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) enzymes as well as absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Besides, two new crystal structures of the compounds have also been reported. In addition, combining the results from the inducible nitric oxide synthase (iNOS), cPLA2, COX-2, and matrix metalloproteinase-9 (MMP-9) enzymatic activity analysis and NO production also confirmed this argument. Overall, the results of this study will be a valuable addition to the growing body of work on biological activities of triazole-based compounds.
AB - Inflammation is a hallmark of many metabolic diseases. We previously showed that ferrocene-appended 1H-1,2,3-triazole hybrids inhibit nitric oxide (NO) production in in vitro models of lipopolysaccharide-induced inflammation in the BV-2 cell. In the present study, we explored the viability, anti-inflammatory, and antioxidant potential of ferrocene-1H-1,2,3-triazole hybrids using biochemical assays in rat mesangial cells (RMCs). We found that, among all the ferrocene-1H-1,2,3-triazole hybrids, X2–X4 exhibited an antioxidant effect on mitochondrial free radicals. Among all the studied compounds, X4 demonstrated the best anti-inflammatory effect on RMCs. These results were supplemented by in silico studies including molecular docking with human cytosolic phospholipase A2 (cPLA2) and cyclooxygenase 2 (COX-2) enzymes as well as absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiling. Besides, two new crystal structures of the compounds have also been reported. In addition, combining the results from the inducible nitric oxide synthase (iNOS), cPLA2, COX-2, and matrix metalloproteinase-9 (MMP-9) enzymatic activity analysis and NO production also confirmed this argument. Overall, the results of this study will be a valuable addition to the growing body of work on biological activities of triazole-based compounds.
KW - Cytosolic phospholipase A (cPLA)
KW - Inducible nitric oxide synthase (iNOS)
KW - Matrix metalloproteinase-9 (MMP-9)
KW - Prostaglandin E (PGE)
KW - Tumor necrosis factor-α (TNF-α)
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U2 - 10.3390/ijms21113823
DO - 10.3390/ijms21113823
M3 - Article
C2 - 32481556
AN - SCOPUS:85085678024
SN - 1661-6596
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
M1 - 3823
ER -