Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine
Journal
European Journal of Medicinal Chemistry
Journal Volume
143
Pages
1942
Date Issued
2018-01-01
Author(s)
Abstract
A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2′-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2′ -amino group with carbamate > amide > urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2′-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2′-(4?-pentynoylamino) 2′-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol. ? 2017 Elsevier Masson SAS
Subjects
Cytotoxicity; Glycoside; Glycosylation; Oleanolic acid
SDGs
Other Subjects
3 o (2' n heptoxycarbonyl 2 deoxy beta d glucopyranosyl) oleanolic acid; alkyl group; amide; antineoplastic agent; carbamic acid; glucosamine; heptane; oleanolic acid derivative; saponin derivative; unclassified drug; urea derivative; antineoplastic agent; glucosamine; oleanolic acid; saponin; alkylation; Article; conjugation; controlled study; cytotoxicity; drug design; drug synthesis; HL-60 cell line; HT-29 cell line; human; human cell; structure activity relation; cell proliferation; chemical structure; chemistry; dose response; drug effects; drug screening; synthesis; tumor cell culture; Antineoplastic Agents; Cell Proliferation; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Glucosamine; Humans; Molecular Structure; Oleanolic Acid; Saponins; Structure-Activity Relationship; Tumor Cells, Cultured
Type
journal article