hrvatski jezikClear Cookie - decide language by browser settings

New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation

Babić, Željka; Crkvenčić, Maja; Rajić, Zrinka; Mikecin, Ana-Matea; Kralj, Marijeta; Balzarini, Jan; Petrova, Mariya; Vanderleyden, Jos; Zorc, Branka (2012) New Sorafenib Derivatives: Synthesis, Antiproliferative Activity Against Tumour Cell Lines and Antimetabolic Evaluation. Molecules, 17 (1). pp. 1124-1137. ISSN 1420-3049

[img]
Preview
PDF - Published Version - article
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (312kB) | Preview

Abstract

Sorafenib is a relatively new cytostatic drug approved for the treatment of renal cell and hepatocellular carcinoma. In this report we describe the synthesis of sorafenib derivatives 4a–e which differ from sorafenib in their amide part. A 4-step synthetic pathway includes preparation of 4-chloropyridine-2-carbonyl chloride hydrochloride (1), 4-chloro-pyridine-2-carboxamides 2a–e, 4-(4-aminophenoxy)-pyridine-2-carboxamides 3a–e and the target compounds 4-[4-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-phenoxy]-pyridine-2-carboxamides 4a–e. All compounds were fully chemically characterized and evaluated for their cytostatic activity against a panel of carcinoma, lymphoma and leukemia tumour cell lines. In addition, their antimetabolic potential was investigated as well. The most prominent antiproliferative activity was obtained for compounds 4a–e (IC50 = 1-4.3 μmol·L−1). Their potency was comparable to the potency of sorafenib, or even better. The compounds inhibited DNA, RNA and protein synthesis to a similar extent and did not discriminate between tumour cell lines and primary fibroblasts in terms of their anti-proliferative activity.

Item Type: Article
Uncontrolled Keywords: sorafenib; amides; cytostatic activity; antimetabolic activity; Caco-2 cells
Subjects: NATURAL SCIENCES > Chemistry
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
BIOMEDICINE AND HEALTHCARE > Pharmacy
Divisions: Division of Molecular Medicine
Projects:
Project titleProject leaderProject codeProject type
Uloga različitih mehanizama odgovora stanica na terapiju oštećenjem DNA-Marijeta Kralj098-0982464-2514MZOS
Sinteza, karakterizacija i djelovanje potencijalnih i poznatih ljekovitih tvari-Branka Zorc006-0000000-3216MZOS
Depositing User: Marijeta Kralj
Date Deposited: 04 Mar 2020 09:29
Last Modified: 04 Mar 2020 09:29
URI: http://fulir.irb.hr/id/eprint/5323
DOI: 10.3390/molecules17011124

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year

Contrast
Increase Font
Decrease Font
Dyslexic Font
Accessibility