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).

Abstract

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.

• Authors: Stefania Aiello, Geoffrey Wells, Erica L Stone, Hachemi Kadri, Rana Bazzi, David R Bell, Malcolm F G Stevens, Charles S Matthews, Tracey D Bradshaw, Andrew D Westwell
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 51 Issue 16 Pg. 5135-9 (Aug 28 2008) ISSN: 1520-4804 [Electronic] United States
• PMID: 18666770 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole
• Antineoplastic Agents
• Benzopyrans
• Benzothiazoles
• Benzoxazoles
• Receptors, Aryl Hydrocarbon

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzopyrans (chemical synthesis, pharmacology)
• Benzothiazoles (chemical synthesis, pharmacology)
• Benzoxazoles (chemical synthesis, pharmacology)
• Breast Neoplasms (drug therapy)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Humans
• Receptors, Aryl Hydrocarbon (metabolism)
• Structure-Activity Relationship