New homocamptothecins: synthesis, antitumor activity, and molecular modeling. Export

@article{citeulike:3740699, abstract = {Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 9l, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity.}, author = {Miao, Z. and Sheng, C. and Zhang, W. and Ji, H. and Zhang, J. and Shao, L. and You, L. and Zhang, M. and Yao, J. and Che, X.}, citeulike-article-id = {3740699}, citeulike-linkout-0 = {http://dx.doi.org/http://dx.doi.org/10.1016/j.bmc.2007.10.046}, citeulike-linkout-1 = {http://dx.doi.org/10.1016/j.bmc.2007.10.046}, doi = {http://dx.doi.org/10.1016/j.bmc.2007.10.046}, journal = {Bioorganic \& medicinal chemistry}, keywords = {camptothecin, coletta, domain, topoisomerase}, month = {February}, number = {3}, pages = {1493--1510}, posted-at = {2008-12-03 15:12:06}, priority = {2}, title = {New homocamptothecins: synthesis, antitumor activity, and molecular modeling.}, url = {http://dx.doi.org/http://dx.doi.org/10.1016/j.bmc.2007.10.046}, volume = {16}, year = {2008} }

TY - JOUR ID - citeulike:3740699 L3 - citeulike-article-id:3740699 N2 - Homocamptothecins (hCPTs) represent a class of new emerging antitumor agents, which contains a seven-membered beta-hydroxylactone in place of the conventional six-membered alpha-hydroxylactone ring (E ring) of camptothecins. Some novel 7-substituted hCPTs were designed and synthesized based on a newly developed synthetic route which couples ring A with ring C, E and D. Most of the synthesized compounds exhibit very high cytotoxic activity on tumor cell line A549. Some compounds, such as 9b, 9l, and 9y, show broad in vitro antitumor spectrum and are more potent than topotecan. Three-dimensional quantitative structure-activity relationship (3D-QSAR) methods, CoMFA and CoMSIA, were applied to explain the structure-activity relationship (SAR) of the synthesized compounds. Furthermore, molecular docking was used to clarify the binding mode of the synthesized compounds to human DNA topoisomerase I. The important hydrophobic, base-pair stacking, and hydrogen-bonding interactions were observed between the hCPT derivatives and their receptor. The results from molecular modeling will guide the design of novel hCPTs with higher antitumor activity. IS - 3 JF - Bioorganic & medicinal chemistry EP - 1510 TI - New homocamptothecins: synthesis, antitumor activity, and molecular modeling. VL - 16 SP - 1493 KW - camptothecin KW - coletta KW - domain KW - topoisomerase AU - Miao, Z AU - Sheng, C AU - Zhang, W AU - Ji, H AU - Zhang, J AU - Shao, L AU - You, L AU - Zhang, M AU - Yao, J AU - Che, X PY - 2008/February// UR - http://dx.doi.org/http://dx.doi.org/10.1016/j.bmc.2007.10.046 ER -