Chemoinformatic Analysis of Isothiocyanates: Their Impact in Nature and Medicine

Abstract

Isothiocyanates (ITCs) have a significant impact on food and natural product chemistry. Several dietary components and food chemicals contain the isothiocyanate moiety. In addition, many ITCs interact with macromolecules of biological relevance, making these compounds relevant for potential therapeutic applications and disease prevention. However, there is a lack of systematic analysis of ITCs in chemical and biological databases. Herein, we conducted a comprehensive analysis of ITCs present in public domain databases, including natural products, food chemicals, macromolecular targets of drugs, and the Protein Data Bank. A total of 154 ITCs were found, which can be classified into seven categories: acyclic, cyclic, polycyclic, aromatic, polyaromatic, indolic, and glycosylated. 24 ITCs were reported in 18 vegetable sources, mainly in cruciferous vegetables (Brassica oleracea L.). Calculated properties of pharmaceutical relevance indicated that 11 % of the 154 ITCs would be suitable to be orally absorbed and 48 % permeate the blood-brain-barrier. It was also found that seven molecular targets have been co-crystallized with ITCs and the most frequent is the macrophage migration inhibitory factor. It is expected that this work will contribute to the sub-disciplines of natural products and food informatics.

Isothiocyanate-Rich Extracts from Cauliflower (Brassica oleracea Var. Botrytis) and Radish (Raphanus sativus) Inhibited Metabolic Activity and Induced ROS in Selected Human HCT116 and HT-29 Colorectal Cancer Cells

“…Further research evaluating the bioaccessibility and bioavailability of the targeted isothiocyanates is encouraged, aiming to evaluate their natural presence under gastrointestinal conditions, potential release, and biological effects. Hence, it has been reported that based on bioinformatic predictions, BITC and AITC, together with phenetyl-isothiocyanate, phenyl-isothiocyanate, 4-isothiocyanabut-1-ene, 7-isothiocyanatohept-1-ene, iberin, and ethyl isothiocyanate, are isothiocyanates with the largest biological spectrum and are promising for pharmacological research [ 76 ].…”

Assessment of Methodological Pipelines for the Determination of Isothiocyanates Derived from Natural Sources

“…The breakdown product of the hydrolysis of GSLs includes a variety of nitrogenous compounds such as ITCs, thiocyanates, nitriles, and epithionitriles, depending on the reaction conditions (i.e., pH, temperature and reducing agents like ferrous ions, ascorbate, etc.) [45][46][47][48][49][50][51][52][53][54]. For instance, thiohydroximate-O-sulphate, at neutral pH, is rearranged into ITCs whereas at low pH it can be rearranged into nitriles (Figure 2) [55][56][57][58][59][60][61].…”

“…In all cases, the rearrangement of thiohydroximate-O-sulphate into its active metabolites is accompanied by loss of a sulphate group. The importance of this class of molecules relies on their anticancer properties by downgrading the factors that are responsible for the cellular detoxification [50,64]. More specifically, ITCs can form an adduct with glutathione (GSH) during the mercapturic acid pathway, causing GSH depletion [65][66][67].…”

“…The nanoformulation of ITCs was acomplished via their encapsulation with either organic (micelle, liposome, dendrimer, polymeric nanoparticles, solid lipoid nanoparticle, and carbon nantube) or inorganic (gold, iron oxide or silicon) nanocarriers [80]. The importance of this class of molecules relies on their anticancer properties by downgrading the factors that are responsible for the cellular detoxification [50,64]. More specifically, ITCs can form an adduct with glutathione (GSH) during the mercapturic acid pathway, causing GSH depletion [65][66][67].…”

Copper Photocatalyzed Divergent Access to Organic Thio- and Isothiocyanates

“…To broaden the scope of this ATRA reaction, we sought to develop a protocol to access isothiocyanates in a subsequent reaction selectively. Given the presence of benzyl isothiocyanates in bioactive molecules and their importance as synthetic intermediates, ,− we targeted the design of a one-pot procedure encompassing sequential ATRA followed by a zinc-mediated isomerization . Gratifyingly, zinc chloride was proven to be an efficient isomerization mediator, promoting one-pot access to isothiocyanates with good overall yields (Scheme a).…”