Document Type : Research Articles
Authors
1
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Egypt,
2
Département of medicinal chemistry, faculty of pharmacy, Minia university, Minia, Egypt.
3
Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia 61519, Egypt
4
Department of Histology and Cell Biology, Faculty of Medicine, Minia University, Egypt
5
Department of Pharmacology, Faculty of Medicine, Minia University, Egypt
6
Department of Medicinal Chemistry, Faculty of Pharmacy, Port Said University
Abstract
Decreasing or inhibiting apoptosis is a therapeutic strategy to reduce the pathological states of diseases like stroke, neurodegeneration, retinal cell death, myocardial and liver ischemia, and inflammatory diseases such as sepsis, osteoarthritis, rheumatoid arthritis, and asthma. This study designed and synthesized a new series of apoptosis inhibitors using a 1,5-diaryl-1,2,4-triazole3-carboxamide scaffold. Compounds 8a, 8b, 9a, 10a, and 10b underwent biochemical, histological, immunohistochemical, and morphometric studies on two vital organs, viz. liver and ovary. In vivo, general biomarkers in the liver and ovary were measured and specific biomarkers were. Different stains such as Perl’s iron stain, H & E stain and immune stain were utilized to evaluate caspase-3 inhibition. The findings are consistent with the docking study, i.e., compounds with two carbon linkers are better than those with longer or shorter ones as antiapoptotic. The most promising compounds 8a and 10a showed the highest potencies and selectivity against caspase-3 amongst other caspases like caspase -7, -8, -9, and 10 that could be considered for further clinical studies.
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