Synthesis of Thiol Derivatives of Biological Active Compounds for Nanotechnology Application

Abstract

An efficient method of thiol group introduction to the structure of common natural products and synthetic active compounds with recognized biological efficacy such genistein (1), 5,11-dimethyl-5H-indolo[2,3-b]quinolin (2), capecitabine (3), diosgenin (4), tigogenin (5), flumethasone (6), fluticasone propionate (7), ursolic acid methyl ester (8), and β-sitosterol (9) was developed. In most cases, the desired compounds were obtained easily via two-step processes involving esterification reaction employing S-trityl protected thioacetic acid and the corresponding hydoxy-derivative, followed by removal of the trityl-protecting group to obtain the final compounds. The results of our preliminary experiments forced us to change the strategy in the case of genistein (1), and the derivatization of diosgenin (4), tigogenin (5), and capecitabine (3) resulted in obtaining different compounds from those designed. Nevertheless, in all above cases we were able to obtain thiol-containing derivatives of selected biological active compounds. Moreover, a modelling study for the two-step thiolation of genistein and some of its derivatives was accomplished using the density functional theory (B3LP). A hypothesis on a possible reason for the unsuccessful deprotection of the thiolated genistein is also presented based on the semiempirical (PM7) calculations. The developed methodology gives access to new sulphur derivatives, which might find a potential therapeutic benefit.

Anti-Cancer and Electrochemical Properties of Thiogenistein—New Biologically Active Compound

“…However, sulfur-containing compounds have been used as excellent ligands for binding to flat gold surfaces as well as gold nanoparticles, because of a very strong interaction of sulfur nucleophiles with gold. Therefore, to increase the strength of the interaction, and improve the stability of AuNPs-GE conjugates, we focused on the investigation of an optimal thiol linker as a new derivative-thiolated genistein (TGE, 7-O-[2-(mercaptomethylcarboxy)ethyl-genistein) described by Sidoryk and co-workers [8] (compound No. 26).…”

Thiogenistein—Antioxidant Chemistry, Antitumor Activity, and Structure Elucidation of New Oxidation Products

“…Flavonoids and isoflavonoids such as genistein (GE) are well-known antioxidants and can help protect cells against reducing carcinogenesis. Flavonoids exhibit a broad spectrum of biological activity, including antioxidant, antitumor, antibacterial, antiviral, anti-inflammatory, anti-allergenic, and vasodilatory actions [ 3 , 4 , 5 , 6 , 7 , 8 ]. Additionally, they play an important role in the prevention and treatment of hormone-dependent diseases.…”

“…Therefore, a lot of studies have focused on obtaining genistein derivatives (mainly modified by glycosylation, alkylation, esterification, and hydroxylation) and their drug delivery systems that achieved the required pharmacological activity but also showed fewer side effects and therapeutic limitations. Thiolated genistein (TGE), described by Sidoryk and co-workers [ 8 ], is composed of the genistein residue bound at the 7-OH site to the hydroxyethyl linker and thioglycolic acid residue. Such a new construction of genistein has several interesting properties.…”

Synthesis and Cytotoxicity of Sulfanyl, Sulfinyl and Sulfonyl Group Containing Ursane Conjugates with 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles

“…Hybrids of triterpenoids with sulfur-containing moieties and versatile heterocyclic substituents have been actively designed and studied to improve the antitumor activity or bioavailability. [6][7][8][9] The conjugates of ursolic acid with sulfurcontaining heterocycles-anetoldithiolthione and lipoic acid (hydrogen sulfide donors) were prepared. [10][11][12] It should be noted that only a few sulfur-containing derivatives of triterpenoids have been prepared, thus, other hybrids of triterpenoids comprising the thione groups, sulfoxides or sulfones, are scarcely known.…”

“…The hybridization of pharmacophores of different nature is a common synthetic methodology applied for the preparation of new bioactive compounds with novel or enhanced bioactivity. Hybrids of triterpenoids with sulfur‐containing moieties and versatile heterocyclic substituents have been actively designed and studied to improve the antitumor activity or bioavailability [6–9] . The conjugates of ursolic acid with sulfur‐containing heterocycles‐ anetoldithiolthione and lipoic acid (hydrogen sulfide donors) were prepared [10–12] .…”