A Study on Synthesis and Antioxidant Activity Comparison of Novel Stilbenebenzamide Compounds.

BACKGROUND: Stilbene phytalexis (1,2-diphenyloethylen) and benzamide are beneficial for human health. To increase the stilbene ring activity, a new series of its derivatives containing benzamide structure was synthesized and evaluated for their in vitro antioxidant power. METHODS: 1H nuclear magnetic resonance, mass spectroscopy, and chromatographic analyses were used to confirm the successful synthesis. The antioxidant properties were determined by the elimination of O2˙-, HO˙ , DPPH˙ , ABTS+˙ radicals, total antioxidant status (TAS) and the ferric reducing antioxidant activities (TAC) measurements. RESULTS: Stilbenebenzamide compounds showed a wide spectrum of antioxidant ability; however, their total antioxidant power was weaker than those of butylated hydroxytoluene (BHT), ascorbic acid, and resveratrol. The highest antiradical activity towards O2˙ and HO˙ was shown by the compounds with structures containing amine group (SBEBA, SBA) (O2˙: 37.7 - 38.0% and 40.8 - 43.5%, HO˙ : 29.8%, 28.7% inhibition, respectively) at1.25 mM concentration. The antiradical power of SBEBA (0.29) in DPPH˙ assay was lower than those of resveratrol (1.83), ascorbic acid (3.63) and BHT (4.09). The TAS values of the synthesized compounds ranged from 152.9±5.3 to 240.2±6.7µM trolox equivalent/gram (TE/g) and were much lower than those of BHT (1304±43.0), reservatrol (1360±29.0) and ascorbic acid (2782±39.7) µM TE/g. Similarly, the TAC values ranging from 29.7±0.9 to 41.5±1.6 µM TE were weaker than that of resveratrol (239.2 ±6.7 µM TE/g). CONCLUSION: The results suggest that the presence of the hydroxyl group in the stilbene ring should be considered in the further design of stilbenebenzamide compounds to enhance their antioxidant activity.

Novel Aryl Substituted Pyrazoles as Small Molecule Inhibitors of Cytochrome P450 CYP121A1: Synthesis and Antimycobacterial Evaluation.

Three series of biarylpyrazole imidazole and triazoles are described, which vary in the linker between the biaryl pyrazole and imidazole/triazole group. The imidazole and triazole series with the short -CH2- linker displayed promising antimycobacterial activity, with the imidazole-CH2- series (7) showing low MIC values (6.25-25 µg/mL), which was also influenced by lipophilicity. Extending the linker to -C(O)NH(CH2)2- resulted in a loss of antimycobacterial activity. The binding affinity of the compounds with CYP121A1 was determined by UV-visible optical titrations with KD values of 2.63, 35.6, and 290 µM, respectively, for the tightest binding compounds 7e, 8b, and 13d from their respective series. Both binding affinity assays and docking studies of the CYP121A1 inhibitors suggest type II indirect binding through interstitial water molecules, with key binding residues Thr77, Val78, Val82, Val83, Met86, Ser237, Gln385, and Arg386, comparable with the binding interactions observed with fluconazole and the natural substrate dicyclotyrosine.