Thiadiazole derivatives as anticancer agents
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REVIEW
Thiadiazole derivatives as anticancer agents Monika Szeliga1 Received: 15 June 2020 / Revised: 13 August 2020 / Accepted: 20 August 2020 © The Author(s) 2020
Abstract In spite of substantial progress made toward understanding cancer pathogenesis, this disease remains one of the leading causes of mortality. Thus, there is an urgent need to develop novel, more effective anticancer therapeutics. Thiadiazole ring is a versatile scaffold widely studied in medicinal chemistry. Mesoionic character of this ring allows thiadiazole-containing compounds to cross cellular membrane and interact strongly with biological targets. Consequently, these compounds exert a broad spectrum of biological activities. This review presents the current state of knowledge on thiadiazole derivatives that demonstrate in vitro and/or in vivo efficacy across the cancer models with an emphasis on targets of action. The influence of the substituent on the compounds’ activity is depicted. Furthermore, the results from clinical trials assessing thiadiazolecontaining drugs in cancer patients are summarized. Keywords Thiadiazole derivatives · Cancer · Anticancer therapy · Clinical trials
Introduction According to the most recent data provided by the International Agency for Research on Cancer (IARC), 18.1 million new cases and 9.6 million cancer deaths were registered worldwide in 2018 [1]. Due to the population aging and growth, the number of new cancer cases is expected to increase. Although a substantial progress was made in the understanding of molecular biology of particular cancer types, and numerous potential specific therapeutic targets were identified in recent years, there is an urgent necessity for the development of improved anticancer therapeutic strategies. Thiadiazole is a five-membered heterocyclic compound containing one sulfur and two nitrogen atoms. It occurs in nature in four isoforms: 1,2,3-thiadiazole, 1,2,4-thiadizaole, 1,2,5-thiadiazole and 1,3,4-thiadiazole (Fig. 1). Taking into account that thiadiazole is the bioisostere of pyrimidine and oxadiazole, it is not surprising that compounds bearing this moiety present a broad spectrum of pharmacological properties, including antiviral, antibacterial, antifungal, * Monika Szeliga [email protected] 1
Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Str, 02‑106 Warsaw, Poland
antiparasitic, anti-inflammatory and anticancer activities [2]. Due to the mesoionic nature, thiadiazoles are able to cross the cellular membranes. Their relatively good liposolubility is most likely attributed to the presence of the sulphur atom [3]. The thiadiazole-containing drugs, including diuretics acetazolamide and methazolamide or antibiotics cefazedone and cefazolin sodium, are already used in clinics. Accumulating evidence has also revealed numerous thiadiazole derivatives that display anticancer activities in various in vitro and in vivo models (summarized in Table 1). Moreover, several thiadiazole-containing compounds hav
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