Journal of Medicinal Chemistry p. 526 - 536 (1995)
Update date:2022-08-17
Topics:
Gandolfi
Beggiolin
Menta
Palumbo
Sissi
Spinelli
Johnson
As part of a program aimed at exploring the effect of the introduction of heteroatoms into the anthracene-9,10-dione chromophore, we have synthesized novel 1,4-bis[(aminoalkyl)amino]-benzo[g]phthalazine-5,10-diones (BPDs) 1 which are related to the antitumor agents ametantrone and mitoxantrone. Derivatives 1 were prepared by chromic acid oxidation of acylated benzo[g]phthalazines 5 followed by acid hydrolysis or by silylation-amination of 5,10-dihydroxybenzo[g]phthalazine-1,4-dione (8). The 1- [(aminoalky])amino]-4-amino congeners 2 were isolated in low yields as byproducts from the oxidation of 5. Against a panel of human tumor cell lines, the benzo[g]phthalazine-5,10-diones 1 and 2 exhibited cytotoxic activity comparable or even superior to that of mitoxantrone. In compounds 1, structure activity relationships different than those operative in the carbocyclic series appeared to emerge. DNA-binding studies with the ametantrone-like compound 1c and its single-armed congener 2c indicated that the introduction of a 2,3-diaza subunit into the anthracene-9,10-dione chromophore reduces the affinity of the drug for DNA in comparison with ametantrone. On the other hand, the number of side-chain groups does not affect binding to a great extent. These findings seem to suggest mechanisms of cell death other than those induced by simple interaction of the 1,4-BPDs 1 and 2 with DNA.
View MoreChangzhou Kingyo Chemical Corporation Ltd.
website:http://www.kingyochem.com
Contact:+86-519-85105717
Address:19# Wuqing North Road, Changzhou , Jiangsu, China
Jiangxi Huashi Pharmaceutical Co., Ltd
Contact:+86-795-4509628
Address:Ningbo Ave., Fengtian Industrial Park, Fengxin Country, Jiangxi, China.
website:http://www.apeptides.com/en/
Contact:+86-21-60871011
Address:No. 80 Chuanshan Shuyuan Steet,Pudong,Shanghai
Contact:+86 21 5017 5386
Address:No 999,Jiangyue Rd, Minhang Dist ,201114,Shanghai ,China
ALPHA PHARMACEUTICAL CO,LTD JIANGSU
Contact:+86-527-84829968,+86-527-84829998
Address:suqian city
Doi:10.1016/j.tet.2018.10.064
(2018)Doi:10.1039/c7cc01283g
(2017)Doi:10.1021/ja0752585
(2007)Doi:10.1002/anie.201913088
(2020)Doi:10.1002/chem.202002696
(2020)Doi:10.1021/ja0394028
(2004)