Design, synthesis and anticancer activity of piperazine hydroxamates and their histone deacetylase (HDAC) inhibitory activity.
Six compounds were synthesized with piperazine in linker region and hydroxamate as Zinc Binding Group (ZBG). They were screened against three cancer cell-lines (NCIH460; HCT116; U251). Compounds 5c and 5f with GI(50) value of 9.33+/-1.3 microM and 12.03+/-4 microM, respectively, were tested for their inhibitory potential on hHDAC8. Compound 5c had IC(50) of 33.67 microM. Compounds were also screened for their anticancer activity against HL60 human promyelocytic leukemia cell line due to the presence of pharmacophoric features of RR inhibitors in them. Compound 5c had IC(50) of 0.6 microM at 48h.
Chetan
Bhadaliya
B
Department of Pharmaceutical Sciences, Birla Institute of Technology, Mesra, Ranchi, Jharkhand, India.
Bunha
Mahesh
M
Jagrat
Monika
M
Sinha
Barij Nayan
BN
Saiko
Philipp
P
Graser
Geraldine
G
Szekeres
Thomas
T
Raman
Ganapathy
G
Rajendran
Praveen
P
Moorthy
Dhatchana
D
Basu
Arijit
A
Jayaprakash
Venkatesan
V
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010879:Piperazines; D000077489:Piperazine; D006655:Histone Deacetylases