Background and Purpose Previous studies have shown that Creosote bush‐derived nordihydroguaiaretic acid (NDGA) exerts beneficial actions on the key components of metabolic syndrome including dyslipidaemia, insulin resistance and hypertension in several relevant rodent models. Here, we synthesized and screened a total of 6 anti‐hyperlipidaemic analogues of NDGA and tested their efficacy against hepatic lipid metabolism in a high‐fructose diet (HFrD) fed dyslipidaemic rat model. Experimental Approach HFrD fed Sprague–Dawley rats treated with NDGA or one of the six analogues were used. Serum samples were analysed for blood metabolites, whereas liver samples were quantified for changes in various mRNA levels by real‐time RT‐PCR. Key Results Oral gavage of HFrD‐fed rats for 4 days with NDGA analogues 1 and 2 (100 mg·kg−1·day−1) suppressed the hepatic triglyceride content, whereas the NDGA analogues 2, 3 and 4, like NDGA, decreased the plasma triglyceride levels by 70–75%. qRT‐PCR measurements demonstrated that among NDGA analogues 1, 2, 4 and 5, analogue 4 was the most effective at inhibiting the mRNA levels of some key enzymes and transcription factors involved in lipogenesis. All four analogues almost equally inhibited the key genes involved in triglyceride synthesis and fatty acid elongation. Unlike NDGA, none of the analogues affected the genes of hepatic fatty acid oxidation or transport. Conclusions and Implications Our data suggest that NDGA analogues 1, 2, 4 and 5, particularly analogue 4, exert their anti‐hyperlipidaemic actions by negatively targeting genes of key enzymes and transcription factors involved in lipogenesis, triglyceride synthesis and fatty acid elongation. These analogues have therapeutic potential.

Global density functional descriptors analysis on a series of chloro- and fluoropyrroles provide vital data concerning their overall biochemical activities. In this study, a comprehensive investigation is presented for a series of chloro- and fluoropyrroles using DFT-based descriptors to elucidate physicochemical properties and their relevance to reactivity, charge transfer, site selectivity, and toxicity. Electrophilicity-based charge transfer (ECT) descriptor reveals the fact that chloro- and fluoropyrroles act as electron donors during their interaction with DNA bases. The local descriptor, namely, multiphilic descriptor conveys the activeness of specific sites in chloro- and fluoropyrroles. Further, Toxicity Prediction Komputer Assisted Technology (TOPKAT) studies on carcinogenicity bioassays using four rodent models provide the interesting fact that chloro- and fluoropyrroles exhibit a strong skin sensitization effect in these species.

No abstract