New thiourea and 1,3‐thiazolidin‐4‐one derivatives effective on the HIV‐1 virus

Abstract

Thiourea derivatives have been reported to possess many biological activities, among them antiviral and antitumoral properties. As part of our continuing effort to develop new active compounds, we report the synthesis and the evaluation of new fifteen thiourea derivatives with 1,3-benzothiazole-2-yl moiety, among them a group of biologically active (1-7) also underwent cyclization to 1,3-thiazolidin-4-ones. Molecular structure of four compounds (4, 13, 15 and 3a) was determined by an X-ray crystallography. We here report the evaluation of their cytotoxicity against human leukaemia/lymphoma- and solid tumour-derived cell lines and of their antiviral activity against HIV-1 and representatives of ssRNA and dsDNA viruses. Derivative 5 showed an interesting activity against HIV-1 wild type and against variants carrying clinically relevant mutations. A colorimetric enzyme immunoassay clarified its mode of action as a non-nucleoside inhibitor of the reverse transcriptase.

Investigation of the Mechanisms of Cytotoxic Activity of 1,3-Disubstituted Thiourea Derivatives

“…The (thio)urea branch is an element of several medicines with anticancer profiles, such as sorafenib, multikinase-inhibitory diarylthiorea derivative, or tenovin-1, the benzylthiourea, which acts as a reversible inhibitor of class III HDAC sirtuins (Figure 1). On the other hand, it was reported that (hetero)aryl terminal fragments of thiourea moiety, enriched with electron-negative substituents, could provide biological responses, not only cytotoxic [2][3][4], but also antibacterial [2][3][4][5][6][7][8], antiviral [2,[9][10][11][12], antimycobacterial [5,13], antioxidant [14], and anti-inflammatory [6] properties, as well as central nervous system activation [15][16][17][18].…”

Synthesis of thiazolidin-4-ones and thiazinan-4-ones from 1-(2-aminoethyl)pyrrolidine as acetylcholinesterase inhibitors

“…Thiazolidinone belongs to this class and is a versatile scaffold to the development of new bioactive compounds. Numerous studies describe a wide range of pharmacological properties of thiazolidinones: anti-HIV 12 , antitumor 13 , 14 , anti-inflammatory 15 , antimicrobial 16 , antihyperglycemic 17 , and acetyl/butyrylcholinesterase inhibition 5 . Thiazinanones (six-membered heterocycle) also show important biological activity such as anticancer 18 , antimalarial 19 , antihypertensive 20 , antibacterial 21 , and antihyperglycemic 17 .…”

G protein‐coupled receptor binding and pharmacological evaluation of indole‐derived thiourea compounds

“…The thiourea branch represents an important synthon, which is responsible for numerous biological activities, such as antimicrobial, antiviral, antiproliferative, and cytotoxic properties . In addition, the class of (thio)urea derivatives were shown to mediate psychotropic‐like effects in rodents.…”