1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones: a novel group of tumour-selective cytotoxins.
Two series of 1-(3-aminomethyl-4-hydroxyphenyl)-3-pyridinyl-2-propen-1-ones, designed as novel cytotoxins, were synthesized. The compounds had low CC50 values in the micromolar range against HL-60 promyelocytic leukemic cells and HSC-2, HSC-3 and HSC-4 oral squamous cell carcinomas. The CC50 values of these compounds were higher towards non-malignant HGF (gingival fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts) cells, which reveals the tumour-selectivity of these enones. A representative compound 4c caused cleavage of PARP1 in HSC-2 cells but not in HGF cells, which may be a contributing factor to the tumour-selectivity.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University , Erzurum , Turkey.
Sinan
S
Bilginer
Halise Inci
HI
Gul
Ebru
E
Mete
Umashankar
U
Das
Hiroshi
H
Sakagami
Naoki
N
Umemura
Jonathan Richard
JR
Dimmock
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D047188:Chalcones; D011725:Pyridines