Synthesis and biological evaluation of a cyclic ether fluorinated noscapine analog.
We present here a novel semi-synthetic cyclic ether fluorinated noscapine analog (CEFNA) that shows potent antiproliferative and anticancer activity in both hormone-responsive (MCF-7) and hormone non-responsive (MDA-MB-231) breast cancer cells. Interestingly, it is also effective against MCF-7/Adr, an adriamycin-resistant variant of MCF-7 cells. Immunofluorescence experiments showed numerous micronuclei, indicative of apoptotic cell death triggered by this novel analog. Mechanistically, CEFNA exerts a strong antimitotic effect as revealed by cell-cycle studies that show a dose-dependent increase in G2/M population preceding a rising sub-G1 population, suggesting apoptosis.
Aneja
Ritu
R
Laboratory for Drug Discovery and Research, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322, USA. raneja@emory.edu
Vangapandu
Surya N
SN
Joshi
Harish C
HC
D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D000996:Antitussive Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D009665:Noscapine / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008941:Spindle Apparatus / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D000996:Antitussive Agents; D004317:Doxorubicin; D009665:Noscapine