Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648).
New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a, b and 12a, d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.
Aiello
Stefania
S
Welsh School of Pharmacy, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff, CF10 3NB, UK.
Wells
Geoffrey
G
Stone
Erica L
EL
Kadri
Hachemi
H
Bazzi
Rana
R
Bell
David R
DR
Stevens
Malcolm F G
MF
Matthews
Charles S
CS
Bradshaw
Tracey D
TD
Westwell
Andrew D
AD
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013329:Structure-Activity Relationship
C507816:2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole; D000970:Antineoplastic Agents; D001578:Benzopyrans; D052160:Benzothiazoles; D001583:Benzoxazoles; D018336:Receptors, Aryl Hydrocarbon