Benzothiazole-containing hydroxamic acids as histone deacetylase inhibitors and antitumor agents.
Data from clinical studies indicate that inhibitors of Class I and Class II histone deacetylase (HDAC) enzymes show great promise for the treatment of cancer. Zolinza (SAHA, Zolinza) was recently approved by the FDA for the treatment of the cutaneous manifestations of cutaneous T-cell lymphoma. As a part of our ongoing effort to identify novel small molecules to target these important enzymes, we have prepared two series of benzothiazole-containing analogues of SAHA. It was found that several compounds with 6C-bridge linking benzothiazole moiety and hydroxamic functional groups showed good inhibition against HDAC3 and 4 at as low as 1 μg/ml and exhibited potent cytotoxicity against five cancer cell lines with average IC(50) values of as low as 0.81 μg/ml, almost equipotent to SAHA.
Hanoi University of Pharmacy, 13-15 Le Thanh Tong, Hanoi, Viet Nam.
Dao Thi Kim
DT
Oanh
Hoang Van
HV
Hai
Sang Ho
SH
Park
Hyun-Jung
HJ
Kim
Byung-Woo
BW
Han
Hyung-Sook
HS
Kim
Jin-Tae
JT
Hong
Sang-Bae
SB
Han
Van Thi My
VT
Hue
Nguyen-Hai
NH
Nam
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles / Q000737:chemistry*; D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003198:Computer Simulation; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077337:Vorinostat; D000099186:Histone Deacetylase 3
D000970:Antineoplastic Agents; D052160:Benzothiazoles; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases; D006877:Hydroxamic Acids; D012097:Repressor Proteins; D000077337:Vorinostat; D000099186:Histone Deacetylase 3; C400300:HDAC4 protein, human; C005465:benzothiazole