Universität zu Köln

Kaur, Jasleen, Tsvetkova, Yoanna, Arroub, Karim, Sahnoun, Sabri, Kiessling, Fabian and Mathur, Sanjay (2017). Synthesis, characterization, and relaxation studies of Gd-DO3A conjugate of chlorambucil as a potential theranostic agent. Chem. Biol. Drug Des., 89 (2). S. 269 - 277. HOBOKEN: WILEY. ISSN 1747-0285

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Abstract

DO3A-based macrocycles serve as attractive templates from which clinically useful theranostic agents can be obtained after coupling with molecular targeted therapeutic drugs. In this study, we describe the chemical synthesis, relaxation, and cytotoxicity studies of a new DO3A conjugate of chlorambucil (CHL) as a magnetic resonance imaging (MRI) theranostic agent. A convenient route of synthesis is reported, which allowed conjugation of the macrocyclic ligand (DO3A) to the chemotherapeutic drug (CHL) via tyrosine for the preparation of an attractive chelate-drug ensemble (DO3A-TR-CHL). The structures of all intermediates and final compound have been determined by H-1, C-13 NMR, and MS. The efficacy of DO3A-TR-CHL as a non-ionic magnetic contrast agent was tested by performing relaxometric studies on its gadolinium complex. The complex exhibited relaxivities (7.11 mm(-1)/s) higher than that of currently used MR contrast agents and showed enhanced contrast in T-1-weighted images. MTT assays revealed that both DO3A-TR-CHL and Gd(III)-DO3A-TR-CHL conjugates exhibited dose-dependent toxicity and an enhanced antiproliferative activity against tumor (A549 and HeLa) cell lines compared to that of parent drug (CHL), thereby demonstrating their potential to be used as a magnetic resonance imaging theranostic for improved molecular imaging and therapy of human cancers.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaur, Jasleen UNSPECIFIED UNSPECIFIED UNSPECIFIED Tsvetkova, Yoanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Arroub, Karim UNSPECIFIED UNSPECIFIED UNSPECIFIED Sahnoun, Sabri UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiessling, Fabian UNSPECIFIED UNSPECIFIED UNSPECIFIED Mathur, Sanjay UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-240837
DOI:	10.1111/cbdd.12827
Journal or Publication Title:	Chem. Biol. Drug Des.
Volume:	89
Number:	2
Page Range:	S. 269 - 277
Date:	2017
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1747-0285
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Inorganic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CONTRAST AGENTS; IN-VITRO; DERIVATIVES Multiple languages Biochemistry & Molecular Biology; Chemistry, Medicinal Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24083