- Discovery and preliminary evaluation of 2-aminobenzamide and hydroxamate derivatives containing 1,2,4-oxadiazole moiety as potent histone deacetylase inhibitors
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Using Entinostat as a lead compound, 2-aminobenzamide and hydroxamate derivatives have been designed and synthesized. The entire target compounds were investigated for their in vitro antiproliferative activities using the MTT-based assay against five human cancer cell lines including U937, A549, NCI-H661, MDA-MB-231 and HCT116. 2-Aminobenzamide series of compounds (10a-10j) demonstrated the most significant inhibition against human acute monocytic myeloid leukemia cell line U937, but no or poor activities against two human lung cancer cell lines. Furthermore, the target compounds were screened for their inhibitory activities against HDAC 1, 2, and 8. 2-Aminobenzamide derivatives (10) manifested a higher selectivity for HDAC 1 over HDAC 2, but were not active against HDAC 8. In contrast, most hydroxamate derivatives (11) inhibit HDAC 8 with lower IC50 values than SAHA and Entinostat. Docking study with selected compounds 10f and 11a revealed that the compounds might bind tightly to the binding pockets in HDAC 2 and HDAC 8, respectively. The results suggest that they may be promising lead compounds for the development of novel anti-tumor drug potentially via inhibiting HDACs.
- Cai, Jin,Wei, Hongtao,Hong, Kwon Ho,Wu, Xiaoqing,Cao, Meng,Zong, Xi,Li, Lushen,Sun, Chunlong,Chen, Junqing,Ji, Min
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- Synthesis and anti-protozoal activity of novel dihydropyrrolo[3,4-d][1,2,3] triazoles
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1,2,4-Oxadiazole and 1,2,3-triazole containing heterocyclic compounds continue to gain interest in synthesis of chemical entities and exhibit various biological activities as anti-protozoal and anti-cancer agents. By using the principle of bioisosterism,
- Dürüst, Yaar,Karaku, Hamza,Kaiser, Marcel,Tasdemir, Deniz
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p. 296 - 304
(2012/03/27)
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- REACTION OF AMIDOXIMES WITH α-CHLOROACID CHLORIDES: NOVEL SYNTHESIS OF 1,2,4-OXADIAZIN-5-ONES
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The reaction of amidoximes with α-chloroacid chlorides gives under thermal reaction conditions 5-(1-chloroalkyl)-1,2,4-oxadiazoles.In presence of a strong base, the reaction follows a different path leading to the formation of 4H-1,2,4-oxadiazin-5(6H)-one
- Hussein, Ahmad Q.
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p. 163 - 173
(2007/10/02)
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