Subject Area物理化学
Structure-Activity Relationships of Potential Anticancer Active Halogenated Cephalomannine Modified at C-3’’ Position
张延延; 葛广波; 马红; 刘勇; 杨凌
Conference Name第三届中日双边药理学和临床药理学会议
Conference Date2007-8-23
Conference Place中国
Funding Organization中国药理学会
Other AbstractPrevious studies identified the halogen bond between Br at C2’’ position from dibromo-cephalomannine and an oxygen atom from β-tubulin, which might enhance the anticancer potential of taxoids. In this study, using a series of novel halogenated cephalomannine possessing Br at C2’’ position, we were concerned by the impact of modification at C3’’ position of taxoids on their cytotoxic profile and the underlying mechanisms were investigated. METHODS DCB6103, DCB6104, DCB6107 and DCB6108 were synthesized and thoroughly characterized. The cytotoxicity of these novel taxoids and paclitaxel against 6 human tumor cell lines, including breast cancer (MCF-7), non-small lung cancer (A549), leukemia (K562), ovarian cancer (OVCAR-3), colon cancer (HT-29), and osteogenic sarcoma (Saos-2) was assayed by SRB method. RESULTS DCB6103 and DCB6104 exhibited a promising response against tested cancer cell lines including MCF-7, K562, OVCAR-3, HT-29 and Saos-2, with an average value of 12nM compared to 5nM for paclitaxel. However, the pattern of DCB6107 and DCB6108 showed 100-to 200-fold loss of activity. All these new taxoids did not show enhanced activity against paclitaxel-resistant cells (A549) held alterations in microtubule dynamics. CONCLUSION Taxoids with certain hydrogen bond donor possessing at C3’’ position exhibited equivalently cytotoxic activity compared to paclitaxel and dihalogenated cephalomannine. However, significant reductions of activity were observed upon replacement of these substitutions with alkoxy. Our results indicate that the hydrogen/halogen bond donor at C3’’ position might be a primary contributor to T-Toxol lattice structure and self-assembly, and suggest novel design possibility for other microtubule-stabilizing compounds. Key words: cephalomannine; taxol; cytotoxic; structure-activity relationships; hydrogen bond.
Document Type会议论文
Corresponding Author杨凌
Recommended Citation
GB/T 7714
张延延,葛广波,马红,等. Structure-Activity Relationships of Potential Anticancer Active Halogenated Cephalomannine Modified at C-3’’ Position[C],2007:361/2.
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