Parallel Synthesis of O‐Phenoxyethyl and O‐Adamantyl N‐acyl Thiocarbamates Endowed with Antiproliferative Activity

Abstract

In order to further explore the antiproliferative properties of O-phenoxyethyl and O-adamantyl acylthiocarbamates (ATCs), a series of 14 derivatives was prepared by a parallel adaptation of a highly convergent one-pot three-step procedure. Ten acylthiocarbamates were selected by the National Cancer Institute drug evaluation program and screened against a panel of 55 to 58 cell lines derived from nine different types of human cancers. In general, the tested compounds showed a widespread micromolar activity with some specificity against leukemia, renal UO-31, central nervous system (CNS) SNB-75, and non-small cell lung HOP-92 cancer cell lines. Bioinformatic COMPARE analyses were carried out to identify possible mechanism(s) of action for acylthiocarbamate antiproliferative activity.

A novel three-component reaction between isocyanides, alcohols or thiols and elemental sulfur: a mild, catalyst-free approach towards O-thiocarbamates and dithiocarbamates

“…O -Thiocarbamates belong to a class of important biologically active molecules, used mainly as fungicides [1–3] in agricultural and pharmaceutical fields. In particular, recently antitumor [4], anesthetic [5] and enzyme inhibitory effects were discovered, including HIV-1 reverse transcriptase inhibition activity [6–11]. Moreover, their utilization as highly regio- and stereoselective organocatalysts in specific types of chemical tranformations [12–17] was introduced, as well.…”

Eco‐Efficient Ultrasonic‐Responsive Synthesis of Primary O‐Alkyl and O‐Aryl Thiocarbamates Using Brønsted Acid Ionic Liquid [H‐NMP][HSO4] in Aqueous Media at Room Temperature

“…Both of naphthol isomers gave the corresponding Othiocarbamates in 69% and 67%, respectively (Table 3, entries A32, A33). Phenols bearing electron withdrawing groups such as fluorine, chlorine or bromine atoms constructed the Othiocarbamates in good yields after 90 min ( Table 3, entries A11- 13). Surprisingly, phenols with strong electron-withdrawing substituents such as NO 2 , CN, COOR, CHO failed to undergo the reaction under the optimized experimental conditions even after 6 h. Most likely, these functional groups decrease the nucleophilicity of phenolic oxygen atom toward effective attack.…”

“…For example, they can be applied as intermediates in organic syntheses such as thiols and heterocyclic compounds production, as a new source of hydrogen sulfide (H 2 S), and as alcohols and amines protecting group . The biological activity of such compounds have been widely studied and some of the most important activities are elastase inhibition, anti‐bacterial, anti‐proliferative, anti‐fungal, anti‐microbial, anti‐inflammatory and analgesic effects . Furthermore, O ‐thiocarbamates have medicinal applications and have been used in cancer and HIV‐1 treatment.…”

“…Thiocarbamates (thiourethanes), especially O-alkyl and O-aryl thiocarbamates constitute important and versatile classes of compounds for a variety of industrial, synthetic, agricultural and medicinal applications. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] They have been extensively used in agriculture as insecticides, [2] herbicides, [3] pesticides [4] and fungicides in agricultural goals. [5] Moreover, they have many different roles in organic chemistry.…”