Redox Active Molecules in Cancer Treatments

Dear Colleagues,

The primary purpose of this Special Issue of Molecules is to present the results of in vitro, in vivo, and/or in silico studies of the biological effects and activities of the redox-active compounds observed in original research studies or collected and discussed in review articles.

It is already accepted that the change of cells' redox status changes their biological setup [[i]]. Accumulation of reactive oxygen species (ROS) leads to oxidative stress and, consequently, activation of redox-sensitive transcription factors, signalling and metabolic pathways, and orchestrated cell death. Antioxidants like some polyphenols, vitamin C, beta carotenes and glutathione have mostly been investigated because of their chemopreventive capabilities and direct and indirect ROS scavenging effects [[ii],[iii],[iv]]. However, recently the interest in pro-oxidant compounds has increased in association with the promotion of regulated death of cancer cells or with the development of novel anticancer approaches based on the selective inhibition of sustained NRF2/KEAP1 pathway in the cancer cells [[v],[vi]].

We would like to you invite to publish in this Special Issue data from original research studies or reviews focusing on chemical and pharmacological aspects of natural and (semi)synthetic molecules that change cellular ROS concentration and can exert antioxidant and/or pro-oxidant cellular effects. Topics include but are not limited to:

• synthesis and modification of small molecular weight redox modulators with potential pharmacological applications, and the optimization of their antioxidant /pro-oxidant properties and ADMET profile
• non-radical targeted scavenging mechanisms of action of redox modulators such as modulators of activities or/and transcription of glutathione peroxidases, catalase, glutathione-S-transferases and superoxide dismutases as well as KEAP1-NRF2 pathway
• antioxidants with chemopreventive effects
• compounds capable of modifying ROS levels and potentiating the effect of anticancer drugs
• molecular sensitizers used in cancer therapy
• redox-active compound affecting regulated cell deaths

[i]. Buettner, G.R.; Wagner, B.A.; Rodgers V.G. Quantitative redox biology: An approach to understand the role of reactive species in defining the cellular redox environment. Cell Biochem. Biophys. 2013, 67(2), 477-483. doi:10.1007/s12013-011-9320-3

[ii]. Stepanić V, Čipak Gašparović A, Gall Trošelj K, Amić D, Žarković N. Selected attributes of polyphenols in targeting oxidative stress in cancer. Curr. Top. Med. Chem. 2015, 15(5), 496-509. doi:10.2174/1568026615666150209123100

[iii]. Harej A, Macan Meščić A, Stepanić V, Klobučar M, Pavelić K, Pavelić Kraljević S, Raić-Malić S. The Antioxidant and Antiproliferative Activities of 1,2,3-Triazolyl-L-Ascorbic Acid Derivatives. Int. J. Mol. Sci. 2019, 20(19), 4735. doi:10.3390/ijms20194735

[iv]. Stepanić, V.; Matijašić, M.; Horvat, T.; Verbanac, D.; Kučerová-Chlupáčová, M.; Saso, L.; Žarković, N. Antioxidant Activities of Alkyl Substituted Pyrazine Derivatives of Chalcones—In Vitro and In Silico Study. Antioxidants 2019, 8, 90. doi:10.3390/antiox8040090

[v]. Perillo, B.; Di Donato, M.; Pezone, A.; Di Zazzo, E.; Giovannelli, P.; Galasso, G.; Castoria, G.; Migliaccio, A. ROS in cancer therapy: the bright side of the moon. Exp. Mol. Med. 2020, 52(2), 192-203. doi:10.1038/s12276-020-0384-2.

[vi]. Panieri, E.; Buha, A.; Telkoparan-Akillilar, P.; Cevik, D.; Kouretas, D.; Veskoukis, A.; Skaperda, Z.; Tsatsakis, A.; Wallace, D.; Suzen, S.; Saso, L. Potential Applications of NRF2 Modulators in Cancer Therapy. Antioxidants 2020, 9(3), 193; doi:10.3390/antiox9030193

Dr. Višnja Stepanić
Dr. Marta Kučerová-Chlupáčová
Guest Editors

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