الفهرس | Only 14 pages are availabe for public view |
Abstract Our reactions afforded new thirty-two new compounds that were not mentioned in the literature. The preparation of the synthesized compounds was monitored by TLC, and structure elucidation was fulfilled based on elemental analyses (C, H, N), IR, 1H NMR, 13C NMR and mass spectroscopy. Twenty-eight compounds were selected by the National Cancer Institute (NCI, USA) under the Developmental Therapeutic Program (DTP) to evaluate their in vitro anticancer activity against tumor cells in full NCI 60 cell panel. The compounds were tested at single dose of 10-5 M. Compound 91a displayed excellent antiproliferative activity against all of the cancer cell lines. Compound 91a was further evaluated for the five-dose assay. Compound 91a displayed remarkable activity against most human tumor cell lines, fifty of them with GI50 values < 3.0 µM. Enzymes inhibition activity against phosphatidylinositol 3-kinases PI3Kγ and PI3Kα were performed for compounds 79b, 91a, and 97b and results showed that all compounds showed good inhibitory activity towards PI3Kγ enzyme especially compounds 91a exhibited the best inhibitory activity. Moreover, all compounds exhibited weak inhibitory activity towards PI3Kα enzyme. Molecular docking study of the synthesized compounds into the binding site of PI3Kγ and exploration of their binding mode and their interaction with the essential amino acids in the active site of the PI3Kγ were performed using molecular operating environment (MOE) software version 2014.09 (Chemical Computing group Inc., Montreal, Quebec, Canada). |