The design and cytotoxic evaluation of some 1-aryl-3-isopropylamino-1-propanone hydrochlorides towards human Huh-7 hepatoma cells
Author
Mete, E.
Gul, H. I.
Cetin Atalay, R.
Das, U.
Sahin, E.
Gul, M.
Kazaz, C.
Dimmock, J. R.
Date
2011Source Title
Archiv der Pharmazie
Print ISSN
0365-6233
Publisher
Wiley
Volume
344
Issue
5
Pages
333 - 339
Language
English
Type
ArticleItem Usage Stats
101
views
views
75
downloads
downloads
Abstract
A series of 1-aryl-3-isopropylamino-1-propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth-inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X-ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5-fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cytotoxic potencies. A number of guidelines for amplification of the project have been formulated. A number of Mannich bases displayed greater potency than the reference drug 5-fluorouracil against human Huh-7 hepatoma cells. In particular, 1i emerged as a lead compound possessing 2.8 fold higher activity than that of the reference drug. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.