| Autor: |
Tantawy AH; Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.; Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan 430070, People's Republic of China.; Department of Chemistry, College of Science, Benha University, Benha 13518, Egypt., El-Behairy MF; Department of Organic and Medicinal Chemistry, Faculty of Pharmacy, University of Sadat City, Sadat City, Menoufiya 32897, Egypt., Abd-Allah WH; Pharmaceutical Chemistry Department, Collage of Pharmaceutical Science and Drug Manufacturing, Misr University for Science and Technology, P.O. 77, 6th of October City, Giza 12568, Egypt., Jiang H; Department of Chemistry, College of Science, Huazhong Agricultural University, Wuhan 430070, People's Republic of China., Wang MQ; Hubei Insect Resources Utilization and Sustainable Pest Management Key Laboratory, College of Plant Science and Technology, Huazhong Agricultural University, Wuhan 430070, People's Republic of China., Marzouk AA; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut 71524, Egypt. |
| Abstrakt: |
Highly fluorinated candidates containing anticancer pharmacophores like thiosemicarbazone ( 5a - e ) and its cyclic analogues hydrazineylidenethiazolidine ( 6a - e ), 2-aminothiadiazole ( 7a - e ), and 2-hydrazineylidenethiazolidin-4-one ( 8a - e ) were synthesized, and their cytotoxic activity was assayed against 60 tumor cell lines. Compounds 6c , 7b , and 8b displayed the most potent activity with lower toxic effects on MCF-10a. In vitro phosphatidylinositol 3-kinase (PI3K) enzyme inhibition was performed. Compound 6c displayed half-maximal inhibitory concentration (IC 50 , μM) values of 5.8, 2.3, and 7.9; compound 7b displayed IC 50 values of 19.4, 30.7, and 73.7; and compound 8b displayed IC 50 values of 77.5, 53.5, and 121.3 for PI3Kα, β, and δ, respectively. Moreover, cell cycle progression caused cell cycle arrest at the S phase for compounds 6c and 8b and at G1/S for compound 7b , while apoptosis was induced. In silico studies; molecular docking; physicochemical parameters; and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis were performed. The results showed that compound 6c is the most potent one with a selectivity index (SI) of 39 and is considered as a latent lead for further optimization of anticancer agents. |
