Publications (3)6.78 Total impact
-
Article: Synthesis and preliminary bioevaluation of novel E-ring modified acetal analog of camptothecin as cytotoxic agents.
[show abstract] [hide abstract]
ABSTRACT: In an effort to improve the metabolic stability of the E-ring and decrease the toxicity of camptothecin (CPT), a novel cytotoxic acetal analog with 21-alkoxy groups was designed and synthesized. The preliminary results revealed that this class of compounds showed superior antiproliferative activity in vitro and moderate in vivo activity, while their topoisomerase I (Topo I) inhibitory activity was weakened significantly. The implications of these results within the current understanding of the structure-activity relationship of camptothecin are analyzed in detail. The obtained information provides insight into the role of the 21-carbonyl group in the binding of CPT to Topo I-DNA complex.European journal of medicinal chemistry 10/2012; 56:1-9. · 3.27 Impact Factor -
Article: Synthesis and biological evaluation of 7-alkenyl homocamptothecins as potent topoisomerase I inhibitors.
[show abstract] [hide abstract]
ABSTRACT: Homocamptothecin (hCPT) is a camptothecin (CPT) derivative with a seven-membered β-hydroxylactone E ring, which shows higher lactone stability and improves topoisomerase I (Topo I) inhibition activity. In an attempt to improve the antitumor activity of homocamptothecins, a series of 7-alkenyl-homocamptothecin derivatives was designed and synthesized based on a semisynthetic route starting from CPT. Most of the synthesized compounds exhibit higher cytotoxic activities on the A-549 tumor cell line than topotecan (TPT). Some compounds such as 2a and 2o show a broad in vitro antitumor spectrum and exhibit superior Topo I-inhibition activity.Chemistry & Biodiversity 06/2012; 9(6):1084-94. · 1.80 Impact Factor -
Article: Synthesis and biological evaluation of novel homocamptothecins conjugating with dihydropyrimidine derivatives as potent topoisomerase I inhibitors.
[show abstract] [hide abstract]
ABSTRACT: Homocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH₂) spacer between the alcohol moiety and carbonyl group of the classical six-membered α-hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7-formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA-MB-435 and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT.Archiv der Pharmazie 09/2011; 344(11):726-34. · 1.71 Impact Factor
Top Journals
Institutions
-
2011–2012
-
Second Military Medical University, Shanghai
Shanghai, Shanghai Shi, China
-