Synthesis of paclitaxel-BGL conjugates

Hisao Nemoto; Ayato Katagiri; Masaki Kamiya; Tomoyuki Kawamura; Tsuyoshi Matsushita; Kosuke Matsumura; Tomohiro Itou; Hatsuhiko Hattori; Miho Tamaki; Keisuke Ishizawa; Licht Miyamoto; Shinji Abe; Koichiro Tsuchiya

doi:10.1016/j.bmc.2012.07.031

Synthesis of paclitaxel-BGL conjugates

Bioorg Med Chem. 2012 Sep 15;20(18):5559-67. doi: 10.1016/j.bmc.2012.07.031. Epub 2012 Jul 25.

Authors

Hisao Nemoto¹, Ayato Katagiri, Masaki Kamiya, Tomoyuki Kawamura, Tsuyoshi Matsushita, Kosuke Matsumura, Tomohiro Itou, Hatsuhiko Hattori, Miho Tamaki, Keisuke Ishizawa, Licht Miyamoto, Shinji Abe, Koichiro Tsuchiya

Affiliation

¹ Department of Pharmaceutical Chemistry, Institute of Health Biosciences, Graduate School of The University of Tokushima, 1-78, Sho-machi, Tokushima 770-8505, Japan. nem@ph.tokushima-u.ac.jp

PMID: 22892212
DOI: 10.1016/j.bmc.2012.07.031

Abstract

Four kinds of symmetrically branched oligoglyceryl trimeric (BGL003)-paclitaxel conjugates and a corresponding heptameric (BGL007) conjugate were synthesized. Molecular weights of all the compounds were less than two times that of paclitaxel. The anti-tumor activity of the most water-soluble BGL003 conjugate was examined and found to be preserved in spite of the chemical modification that is displacement of the N3'-debenzoyl residue with the BGL003 succinyl residue.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemical synthesis*
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Line, Tumor
Dose-Response Relationship, Drug
Glycerol / chemistry*
Glycerol / pharmacology*
Humans
Male
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Conformation
Molecular Weight
Neoplasms, Experimental / drug therapy*
Paclitaxel / chemistry*
Paclitaxel / pharmacology*
Solubility
Structure-Activity Relationship
Xenograft Model Antitumor Assays

Substances

Antineoplastic Agents, Phytogenic
Paclitaxel
Glycerol