Synthesis and in vitro antitumor activity of novel acylspermidine derivative N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide (AAHD) against HepG2 cells.

Autor: Al-Malki AL; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Bioactive Natural Products Research Group, King Abdulaziz University, Jeddah, Saudi Arabia., Razvi SS; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Mohammed FA; Department of Biology, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Zamzami MA; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Choudhry H; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Kumosani TA; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Production of Bioproducts for Industrial Applications Research Group, King Abdulaziz University, Jeddah, Saudi Arabia., Balamash KS; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Alshubaily FA; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., ALGhamdi SA; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Abualnaja KO; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Bioactive Natural Products Research Group, King Abdulaziz University, Jeddah, Saudi Arabia., Abdulaal WH; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Zeyadi MA; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Al-Zahrani MH; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia., Alhosin M; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer Metabolism and Epigenetic Unit, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia., Asami T; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Graduate School of Agricultural and Life Sciences, University of Tokyo, Bunkyo, Tokyo 113-8657, Japan. Electronic address: asami@mail.ecc.u-tokyo.ac.jp., Moselhy SS; Department of Biochemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia; Experimental Biochemistry Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; Bioactive Natural Products Research Group, King Abdulaziz University, Jeddah, Saudi Arabia; Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt. Electronic address: moselhy6@hotmail.com.
Jazyk: angličtina
Zdroj: Bioorganic chemistry [Bioorg Chem] 2019 Jul; Vol. 88, pp. 102937. Date of Electronic Publication: 2019 Apr 16.
DOI: 10.1016/j.bioorg.2019.102937
Abstrakt: Naturally occurring polyamines like Putrescine, Spermidine, and Spermine are polycations which bind to the DNA, hence stabilizing it and promoting the essential cellular processes. Many synthetic polyamine analogues have been synthesized in the past few years, which have shown cytotoxic effects on different tumours. In the present study, we evaluated the antiproliferative effect of a novel, acylspermidine derivative, (N-(4-aminobutyl)-N-(3-aminopropyl)-8-hydroxy-dodecanamide) (AAHD) on HepG2 cells. Fluorescence staining was performed with nuclear stain (Hoechst 33342) and acridine orange/ethidium bromide double staining. Dose and the time-dependent antiproliferative effect were observed by WST-1 assays, and radical scavenging activity was measured by ROS. Morphological changes such as cell shrinkage & blebbing were analyzed by fluorescent microscopy. It was found that AAHD markedly suppressed the growth of HepG2 cells in a dose- and time-dependent manner. It was also noted that the modulation of ROS levels confirmed the radical scavenging activity. In the near future, AAHD can be a promising drug candidate in chalking out a neoplastic strategy to control the proliferation of tumour cells. This study indicated that AAHD induced anti-proliferative and pro-apoptotic activities on HCC. Since AAHD was active at micromolar concentrations without any adverse effects on the healthy cells (Fibroblasts), it is worthy of further clinical investigations.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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