Identification of biphenyl-based hybrid molecules able to decrease the intracellular level of Bcl-2 protein in Bcl-2 overexpressing leukemia cells.
With the aim of enhancing the structural complexity and diversity of an existing collection of bi- and terphenyl compounds, we synthesized hybrid molecules comprising of spirocyclic ketones (a complexity-bearing core) and bi/terphenyls (privileged fragments). Compounds 1, 3, 4, and 6 showed well-defined activity on apoptosis and differentiation, making them potential leads for development as new anticancer agents and chemical probes to study signaling networks in neoplastic cells.
Pizzirani
Daniela
D
Department of Chemistry and Chemical Biology, Harvard University and the Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02138, USA.
Roberti
Marinella
M
Grimaudo
Stefania
S
Di Cristina
Antonietta
A
Pipitone
Rosaria Maria
RM
Tolomeo
Manlio
M
Recanatini
Maurizio
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001713:Biphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D007659:Ketones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013730:Terphenyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D007659:Ketones; D019253:Proto-Oncogene Proteins c-bcl-2; D013141:Spiro Compounds; D013730:Terphenyl Compounds