title: Synthesis and studies of anticancer properties of lupane-type triterpenoid derivatives containing a cisplatin fragment.
abstract: Both betulinic acid 1 and cisplatin are promising antitumor agents, which induce apoptotic cell death of cancer cells. In the present investigation a new series of betulinic acid-cisplatin conjugates were synthesized and cytotoxicity and selectivity were assessed against five different tumor cell lines. The aim was to combine two structural units, both related with apoptosis induction. The derivatives exerted a dose-dependent antiproliferative action at micromolar concentrations and the effect of these structural variations on anticancer activity was studied and discussed. Several compounds revealed significant antitumor activity, as the most active substance 3-O-acetylbetulinic (2-(2-aminoethyl)aminoethyl)amide (IC50=1.30-2.24 μM). Interestingly, Betulinic acid-cisplatin conjugates were less cytotoxic than the precursors.
authors.affiliation: Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Emmerich
authors.affiliation: Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany.
authors.forename: Kranthi
authors.initials: K
authors.lastname: Vanchanagiri
authors.affiliation: Programa de Pós-graduação em Ciências Farmacêuticas, Universidade Federal do Paraná, Centro Politécnico, 81531-970 Curitiba, PR, Brazil.
authors.forename: Leopoldo C
authors.initials: LC
authors.lastname: Baratto
authors.affiliation: Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Straße 2, 06120 Halle (Saale), Germany.
authors.forename: Harry
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Biozentrum, Martin-Luther-Universität Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany. Electronic address: reinhard.paschke@biozentrum.uni-halle.de.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Paschke
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C480546:lupane; D002945:Cisplatin; D000094062:Betulinic Acid
keywords: Antitumor agent; Betulinic acid derivatives; Cisplatin conjugates; Cytotoxicity; SRB assay