Design, synthesis and biological evaluation of certain 1,3,4-thiadiazine derivatives / Abdelsalam Mohamed Abdelsalam Auf ; Supervised Fatma Abdelfattah Ragab , Salah Abdelmuttalib Abdelaziz , Heba Abdelrasheed Abdelkhalek Allam

Thesis (M.Sc.) - Cairo University - Faculty of Pharmacy - Department of Pharmaceutical Chemistry

According to the anticancer activity exhibited by 1,3,4-thiadiazine, thiourea and oxadiazole derivatives, several novel 1,3,4-thiadiazine hybrids containing thiourea or 1,3,4-oxadiazole moieties have been designed and synthesized. The newly synthesized hybrids were investigated for their in vitro cytotoxic activity against Non-Small Cell Lung Cancer cells (A549 cell line) by MTT bioassay. Compounds 5d, 5i, 5j, 5l, 11d, 11f, 11g and 11h showed the highest cytotoxic activity with IC₅₀ range 0.27-0.97oM. These compounds have been chosen for vascular endothelial growth factor receptor 2 (VEGFR2) enzyme inhibition assay using sorafenib as a reference drug. All the tested compounds showed good inhibition of the level of the enzyme. Compounds 5j and 11g showed the highest inhibition value with IC₅₀ 22.9 and 46.3 nM which were about 3.9 and 1.9 times respectively, more active than sorafenib (90.9 nM). Additionally 5j and 11g showed good inhibitory activity against B-RAF with IC₅₀ 178 and 44.29 nM, respectively )sorafenib 43.80 nM) and against MMP9 with IC50 75.03 and 17.00 nM, respectively

Issued also as CD