Novel rhodanine derivatives induce growth inhibition followed by apoptosis.
We have designed and synthesized three novel compounds, 5-isopropylidiene derivatives of 3-dimethyl-2-thio-hydantoin (ITH-1), 3-ethyl-2-thio-2,4-oxazolidinedione (ITO-1), and 5-benzilidene-3-ethyl rhodanine (BTR-1), and have tested their chemotherapeutic properties. Our results showed that all three compounds induced cytotoxicity in a time- and concentration-dependent manner on leukemic cell line, CEM. Among the compounds tested, BTR-1 was 5- to 7-fold more potent than ITH-1 and ITO-1 when compared by trypan blue and MTT assays. IC(50) value of BTR-1 was estimated to be <10μM. Both cell cycle analysis and tritiated thymidine assays revealed that BTR-1 affects DNA replication by inducing a block at S phase. BTR-1 treatment led to increased level of ROS production and DNA strand breaks suggesting activation of apoptosis for induction of cell death.
Moorthy
Balaji T
BT
Department of Biochemistry, Indian Institute of Science, Bangalore 560 012, India.
Ravi
Subban
S
Srivastava
Mrinal
M
Chiruvella
Kishore K
KK
Hemlal
H
H
Joy
Omana
O
Raghavan
Sathees C
SC
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000648:ultrastructure; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D017382:Reactive Oxygen Species; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue
D000970:Antineoplastic Agents; D004396:Coloring Agents; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; D012236:Rhodanine; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; D014343:Trypan Blue