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Zhu L.,Shanghai University | Zhang X.,Shanghai University | Lei N.,Lian Yun Gang JARI Pharmaceutical Co. | Liu W.,Shanghai University | And 8 more authors.
Chemistry and Biodiversity | Year: 2012

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. © 2012 Verlag Helvetica Chimica Acta AG. Source

Zhu L.,Shanghai University | Zhuang C.,Shanghai University | Lei N.,Lian Yun Gang JARI Pharmaceutical Co. | Guo Z.,Shanghai University | And 7 more authors.
European Journal of Medicinal Chemistry | Year: 2012

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. © 2012 Elsevier Masson SAS. All rights reserved. Source

Zhu L.,Shanghai University | Lei N.,Lian Yun Gang JARI Pharmaceutical Co. | Miao Z.,Shanghai University | Sheng C.,Shanghai University | And 3 more authors.
Chinese Journal of Chemistry | Year: 2012

A mild and efficient Knoevenagel-Doebner reaction from malonic acid and a wide range of aldehydes was catalyzed by a catalytic system consisting of β-alanine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affording the corresponding (E)-α,β-unsaturated carboxylic acids in good to excellent yields and with high stereoselectivity. The advantage of the method is that the reaction could proceed smoothly at ambient temperature so that it can tolerate a variety of functional groups and avoid unnecessary side reactions. Copyright © 2012 SIOC, CAS, Shanghai & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Zhu L.-J.,Shanghai University | Zhuang C.-L.,Shanghai University | Lei N.,Lian Yun Gang JARI Pharmaceutical Co. | Sheng C.-Q.,Shanghai University | And 5 more authors.
Australian Journal of Chemistry | Year: 2011

Homocamptothecins (hCPT) represent a new generation of antitumour agents targeting DNA topoisomerase I. The expanded seven-membered lactone E-ring that characterizes hCPT enhances the plasma stability of the drug and reinforces the inhibition of topoisomerase I (Topo I) compared with conventional six-membered CPT. In an attempt to improve the antitumour activity of hCP, a series of novel hCPT derivatives conjugating with dihydropyridine derivates were designed and synthesized based on a synthetic route that couples 7-formylhomocamptothecin with different dihydropyridine derivates. Most of the synthesized compounds exhibited good cytotoxic activity on tumour cell line A549, MDA-MB-435, and HCT116. Furthermore, this class of compounds showed superior Topo I inhibition activity comparable to or higher than CPT. © CSIRO 2011. Source

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