Design, synthesis and antiproliferative activity of some 3-benzylidene-2,3-dihydro-1-benzopyran-4-ones which display selective toxicity for malignant cells.
A series of 3-benzylidene-4-chromanones 1a-l were prepared and their cytotoxicity towards human Molt 4/C8 and CEM T-lymphocytes as well as murine L1210 lymphoid leukemia cells were compared to the previously generated biodata in these three assays for the isosteric 2-benzylidene-1-tetralones 2a-l. Over 40% of the compounds in series 1 were more potent than their counterparts in series 2, while equipotency was noted in one-third of the comparisons made. In general the IC(50) values of 1a-l towards the human T-lymphocytes were in the low micromolar range. Molecular modelling revealed differences in shapes of representative molecules in series 1 and 2 which may contribute to the variation in cytotoxic potencies. Most of the compounds in series 1 displayed greater potencies towards HSC-2, HSC-3, HSC-4 and HL-60 neoplasms than HGF, HPC, and HPLF normal cells and were well tolerated in mice.
Perjési
Pal
P
Institute of Pharmaceutical Chemistry, University of Pécs, P.O. Box 99, H-7602 Pécs, Hungary.
Das
Umashankar
U
De Clercq
Erik
E
Balzarini
Jan
J
Kawase
Masame
M
Sakagami
Hiroshi
H
Stables
James P
JP
Lorand
Tamas
T
Rozmer
Zsuzsanna
Z
Dimmock
Jonathan R
JR
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D007939:Leukemia L1210 / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects; D013329:Structure-Activity Relationship; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001578:Benzopyrans
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