Synthesis of Pyridine-Dicarboxamide-Cyclohexanone Derivatives: Anticancer and α-Glucosidase Inhibitory Activities and In Silico Study

Molecules

AbdullahMohammed Al-Majid¹  M. Ali¹  Saleh Atef¹  Assem Barakat¹  MohammadShahidul Islam¹  FardousF. El-Senduny²  YaseenA. M. M. Elshaier³  A.F. M. Motiur Rahman⁴  FaridA. Badria⁵ 

[1] Department of Chemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11451, Saudi Arabia;Department of Chemistry, Faculty of Science, Mansura University, Mansura 35516, Egypt;Department of Organic and Medicinal chemistry, Faculty of Pharmacy, University of Sadat City, Menofia 32958, Egypt;Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia;Department of Pharmacognosy, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;

关键词: malonamide;    Michael addition reaction;    cytotoxicity;    cancer;    α-glucosidase;    docking;   

DOI  :  10.3390/molecules24071332

来源: DOAJ

【 摘 要 】

An efficient and practical method for the synthesis of 2,6-diaryl-4-oxo-N,N′-di(pyridin-2-yl)cyclohexane-1,1-dicarboxamide is described in this present study, which occurs through a double Michael addition reaction between diamide and various dibenzalacetones. The reaction was carried out in dichloromethane (DCM) in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The anticancer activities of the synthesized compounds were evaluated in several cancer cell lines, including MCF-7, MDA-MB-231, SAS, PC-3, HCT-116, HuH-7 and HepG2 cells. From these experiments, we determined that MDA-MB-231 was the most sensitive cancer cell line to the compounds 3c, 3e, 3d, 3j and 3l, which exhibited variable anticancer activities (3l [IC₅₀ = 5 ± 0.25 µM] > 3e [IC₅₀ = 5 ± 0.5 µM] > 3c [IC₅₀ = 7 ± 1.12 µM] > 3d [IC₅₀ = 18 ± 0.87 µM] > 3j [IC₅₀ = 45 ± 3 µM]). Of these, 3l (substituted p-trifluoromethylphenyl and chloropyridine) showed good potency (IC₅₀ = 6 ± 0.78 µM) against HCT-116 colorectal cancer cells and exhibited high toxicity against HuH-7 liver cancer cells (IC₅₀ = 4.5 ± 0.3 µM). These values were three times higher than the values reported for cisplatin (IC₅₀ of 8 ± 0.76 and 14.7 ± 0.5 µM against HCT-116 and HuH-7 cells, respectively). The highest α-glucosidase inhibitory activity was detected for the 3d, 3i and 3j compounds. The details of the binding mode of the active compounds were clarified by molecular docking studies.

【 授权许可】

Unknown