Structure-based design and synthesis of novel pseudosaccharine derivatives as antiproliferative agents and kinase inhibitors.
This study is concerned with the implementation of structure-based techniques for the design of new heterocyclic compounds based on pseudosaccharine scaffold with protein kinase inhibition activity. This nucleus was exploited based on the well-known quinazoline core and its interactions with several protein kinases. Two series of compounds employing this new scaffold were synthesized and evaluated at enzymatic and cellular levels. Compound 9b displayed broad spectrum antiproliferative activity on NCI 60-cell lines panel with mean GI50 of 5.4 μM. Investigation of the molecular mechanism showed probable inhibitory activity against Src kinase.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ain Shams University, Abbassia, Cairo, Egypt.
Mohamed S A
MS
Elsayed
Moustafa E
ME
El-Araby
Rabah A T
RA
Serya
Ahmed H
AH
El-Khatib
Michael W
MW
Linscheid
Khaled A M
KA
Abouzid
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D003499:Cyclic S-Oxides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013329:Structure-Activity Relationship
C000591016:1-(4-chlorophenyl)-3-(3-((2,4-dichlorophenyl)amino)-1,1-dioxidobenzo(d)isothiazol-5-yl)urea; D000970:Antineoplastic Agents; D003499:Cyclic S-Oxides; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases