Glutathione-Garlic Sulfur Conjugates: Slow Hydrogen Sulfide Releasing Agents for Therapeutic Applications

Molecules

Ashif Iqbal Bhuiyan²  Vilma Toska Papajani¹  Maurizio Paci²  Sonia Melino²  Noriyuki Nagahara³ 

[1] Department of Professional Chemistries and Pharmacognosy, University of Medicine, Tirana, Str. “Dibra”, Nr. 371, Tirana 1000, Albania; E-Mail:;Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy; E-Mails:Department of Chemical Sciences and Technologies, University of Rome Tor Vergata, via della Ricerca Scientifica, Rome 00133, Italy;

关键词: garlic;    hydrogen sulfide;    allyl sulfur compounds;    sulfurtransferase;    tumor cells;    extraction;    sulfur conjugates;   

DOI  :  10.3390/molecules20011731

来源: mdpi

【 摘 要 】

Natural organosulfur compounds (OSCs) from Allium sativum L. display antioxidant and chemo-sensitization properties, including the in vitro inhibition of tumor cell proliferation through the induction of apoptosis. Garlic water- and oil-soluble allyl sulfur compounds show distinct properties and the capability to inhibit the proliferation of tumor cells. In the present study, we optimized a new protocol for the extraction of water-soluble compounds from garlic at low temperatures and the production of glutathionyl-OSC conjugates during the extraction. Spontaneously, Cys/GSH-mixed-disulfide conjugates are produced by in vivo metabolism of OSCs and represent active molecules able to affect cellular metabolism. Water-soluble extracts, with (GSGaWS) or without (GaWS) glutathione conjugates, were here produced and tested for their ability to release hydrogen sulfide (H₂S), also in the presence of reductants and of thiosulfate:cyanide sulfurtransferase (TST) enzyme. Thus, the TST catalysis of the H₂S-release from garlic OSCs and their conjugates has been investigated by molecular in vitro experiments. The antiproliferative properties of these extracts on the human T-cell lymphoma cell line, HuT 78, were observed and related to histone hyperacetylation and downregulation of GAPDH expression. Altogether, the results presented here pave the way for the production of a GSGaWS as new, slowly-releasing hydrogen sulfide extract for potential therapeutic applications.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.