Journal of Medicinal Chemistry p. 660 - 667 (1985)
Update date:2022-08-03
Topics:
Rosowsky
Freisheim
Bader
Forsch
Susten
Cucchi
γ-tert-Butylaminopterin (γ-tBAMT), the first example of an aminopterin (AMT) γ-monoester, was synthesized, and new routes to the known N10-methyl analogue γ-tert-butyl methotrexate (γ-tBMTX were developed. The inhibitory effects of γ-tBAMT on the activity of purified dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of L1210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of several lines of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of γ-tBMTX and the parent acids AMT and methotrexate (MTX). Patterns of cross-resistance to γ-tBAMT, γ-tBMTX, and AMT among several MTX-resistant cell lines were examined. In vivo antitumor activities of γ-tBAMT and γ-tBMTX were compared in mice with L1210 leukemia. While the activity of γ-tBAMT was very close to that of γ-tBMTX in the DHFR inhibition assay, the AMT ester was more potent than the MTX ester against cells in culture and against L1210 leukemia in vivo. Only partial cross-resistance was shown against γ-tBMTX and γ-tBAMT in cultured cells that were resistant to MTX by virtue of a transport defect or a combination of defective transport and elevated DHFR activity.
View MoreSHENZHEN PENGCHENG REDSTAR INDUSTRY CO.,LTD
Contact:+86-755-82412922
Address:Room 8066, East Block, Square City, Jiabin Road, Luohu District
Contact:86-898-65311214
Address:Room 102, BLDG. 68 Jiangnan City, No. 66 Heping Road,Haikou, Hainan, China
Shaanxi Lighte Optoelectronics Material Co., Ltd.
Contact:+86-29-88320728-622/619/620
Address:No.55 INDUSTRY ROAD 2,XI'AN NATIONAL CIVIL AEROSPACE INDUSTRIAL PARK.XI'AN China 710065.
Zhejiang Chemicals Import & Export Corporation
Contact:86-571-87043088
Address:No.37,Qingchun Road,Hangzhou,China
Hebei Kangtai Pharmaceutical Co.,Ltd
Contact:+86-0317-3512963
Address:Wugang Road,Mengcun of Cangzhou City,Hebei Province ,China
Doi:10.1080/07328300701609111
(2007)Doi:10.1055/s-2007-984899
(2007)Doi:10.1021/ja00296a016
(1985)Doi:10.1016/j.bmcl.2013.03.064
(2013)Doi:10.1016/j.inoche.2006.10.014
(2007)Doi:10.1016/0584-8539(94)E0059-J
(1994)