Dithiolethiones: A Privileged Pharmacophore for Anticancer Therapy and Chemoprevention

Abstract

Dithiolethiones are five-membered sulfur-containing cyclic scaffolds that exhibit antioxidative, anti-inflammatory, antithrombic and chemotherapeutic activities. Dithiolethiones display the chemopreventive and cytoprotective effects by activating the antioxidant response element and mounting the transcription of cytoprotective phase II enzymatic machinery. In addition, several classes of dithiolethiones efficiently modulate the activities of proteins that play crucial roles in normal and cancer cells, including glutathione S-transferase, cyclooxygenases and master regulator NF-κB. The present paper summarizes synthetic aspects, pharmacological potentials and biological attributes of dithiolethiones and its derivatives. Additionally, this review concludes with a discussion on how the current state-of-the-art technologies may help in defining a structure-activity relationship of dithiolethiones, thereby facilitating the design and synthesis of potent drug candidates.

Synthesis and biological activities of novel trifluoromethylpyridine amide derivatives containing sulfur moieties

“…It can be found in many secondary metabolites in living organisms, and exits also in many bio-active compounds ( Fig. 1) with broaden biological activities, [7][8][9][10][11][12][13][14] especially using for anticancer, [15][16][17][18] anti-HIV, 19,20 and treating acid-related disorder, 21 and also using for the inhibitors of topoisomerase 1, 22 anhydrase II, 23 mutated B-Raf, 24,25 cyclooxygenase-2. 26,27 Particularly, compounds containing thioether, sulfone or sulfoxide moieties could exhibit signicantly anti-bacterial, [28][29][30][31][32] anti-fungal, 33,34 herbicidal 35 and insecticidal 36,37 activities for crop protection.…”

Mechanism of H2S Formation from the Metabolism of Anetholedithiolethione and Anetholedithiolone by Rat Liver Microsomes

“…1) is a drug that has been used for many years for its choleretic and sialogogic properties (Christen, 1995;Hamada et al, 1999;Nagano and Takeyama, 2001). ADT and several dithiolethiones are also tested as cancer chemoprevention agents whose mechanisms of action involve activation of Nrf2 signaling and induction of phase 2 enzymes (Zhang and Munday, 2008;Ansari et al, 2018). ADT and its O-demethylated derivative dmADT were also extensively used as H 2 S donors, and the coupling of dmADT with numerous anti-inflammatory drugs has led to a variety of compounds described for their H 2 S-donor properties and therapeutic effects (Li et al, 2007;Chen et al, 2010;Lee et al, 2010;Sparatore et al, 2011;Kashfi and Olson, 2013;Couto et al, 2015;Szabo and Papapetropoulos, 2017;Ansari et al, 2018;Powell et al, 2018).…”

“…ADT and several dithiolethiones are also tested as cancer chemoprevention agents whose mechanisms of action involve activation of Nrf2 signaling and induction of phase 2 enzymes (Zhang and Munday, 2008;Ansari et al, 2018). ADT and its O-demethylated derivative dmADT were also extensively used as H 2 S donors, and the coupling of dmADT with numerous anti-inflammatory drugs has led to a variety of compounds described for their H 2 S-donor properties and therapeutic effects (Li et al, 2007;Chen et al, 2010;Lee et al, 2010;Sparatore et al, 2011;Kashfi and Olson, 2013;Couto et al, 2015;Szabo and Papapetropoulos, 2017;Ansari et al, 2018;Powell et al, 2018). However, the mechanism of H 2 S formation from ADT, dmADT, and their derivatives under biologic conditions remains almost completely unknown (Szabo and Papapetropoulos, 2017;Ansari et al, 2018;Powell et al, 2018).…”

Cavin3 Suppresses Breast Cancer Metastasis via Inhibiting AKT Pathway

“…Meanwhile, both the demethylation drug Decitabine (methylation inhibitor 5-aza-2'-deoxycytidine) and chemopreventive agent Anethole Dithiolethione could restore cavin3 expression (Primiano et al, 1996;Moutinho et al, 2014). Actually, many clinical trials concerning cancer treatment or prevention of these two drugs are ongoing (Nervi et al, 2015;Ramakrishnan et al, 2017;Ansari et al, 2018), which makes cavin3 a promising target for the development of new and more efficient therapies.…”