The natural product molecule 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) isolated from the medicinal plant Melicope ptelefolia was shown to exhibit potent lipoxygenase (LOX) inhibitory activity. It is known that LOX plays an important role in inflammatory response as it catalyzes the oxidation of unsaturated fatty acids, such as linoleic acid to form hydroperoxides. The search for selective LOX inhibitors may provide new therapeutic approach for inflammatory diseases. Herein, we report the synthesis of tHGA analogs using simple Friedel-Craft acylation and alkylation reactions with the aim of obtaining a better insight into the structure-activity relationships of the compounds. All the synthesized analogs showed potent soybean 15-LOX inhibitory activity in a dose-dependent manner (IC₅₀ = 10.31–27.61 μM) where compound 3e was two-fold more active than tHGA. Molecular docking was then applied to reveal the important binding interactions of compound 3e in soybean 15-LOX binding site. The findings suggest that the presence of longer acyl bearing aliphatic chain (5Cs) and aromatic groups could significantly affect the enzymatic activity.

Purpose: Moringa oleifera(MO) is a herbal remedy that is rich in essential amino acids and phytochemicals in the leaves, seeds and pods. It is becoming a famous food in various ethnic groups, and the consumption is increasing worldwide. However, there is no safety profile of the hydroalcoholic MO leaf extracts, or documented teratogenicity aspect. This study was sought to compare the antioxidant activity and the teratogenicity of hydroalcoholic MO leaf extracts in the zebrafish embryo.Design/methodology/approach: MO leaves were extracted with aqueous alcohols (ethanol or methanol: water, 80:20 v/v) using the Soxhlet method. The antioxidant capacity was determined using DPPH assay. The concentrations of extracts ranging from 3 to 1,000 µg/mL were used to examine the toxicity and teratogenicity on the zebrafish embryo.Findings: Both hydroalcoholic MO leaf extracts were positive for alkaloids, terpenoids, steroids, tannins, flavonoids, phenols, coumarins, quinones and glycosides, except saponins only absent in aqueous methanol extract. The antioxidant capacity based on lC₅₀, was 15.92 ± 3.62 mg/mL for aqueous methanolic and 25.28 ± 2.89 mg/mL for aqueous ethanolic extract. For acute toxicity, the aqueous methanolic extract has lower LC₅₀(163.87 ± 12.88 µg/mL) compared to aqueous ethanolic extract (337.48 ± 30.04 µg/mL). The embryo treated with aqueous methanolic extract showed phenotypic defect but not on the aqueous ethanolic extract.Originality/value: This study suggests that aqueous methanol of MO leaves extract has better antioxidant capacity compared to ethanol, and ethanolic leaf extract is safer (higher LC50 and no teratogenicity) than methanolic extract.

A new series of 2,4,6-trihydroxy-3-geranyl-acetophenone (tHGA) analogues were synthesized and evaluated for their lipoxygenase (LOX) inhibitory activity. Prenylated analogues 4a–g (half maximal inhibitory concentration (IC₅₀) values ranging from 35 $\mathsf{\mu }$ M to 95 $\mathsf{\mu }$ M) did not exhibit better inhibitory activity than tHGA (3a) (IC₅₀ value: 23.6 $\mathsf{\mu }$ M) due to the reduction in hydrophobic interaction when the alkyl chain length was reduced. One geranylated analogue, 3d, with an IC₅₀ value of 15.3 $\mathsf{\mu }$ M, exhibited better LOX inhibitory activity when compared to tHGA (3a), which was in agreement with our previous findings. Kinetics study showed that the most active analogue (3e) and tHGA (3a) acted as competitive inhibitors. The combination of in silico approaches of molecular docking and molecular dynamic simulation revealed that the lipophilic nature of these analogues further enhanced the LOX inhibitory activity. Based on absorption, distribution, metabolism, excretion, and toxicity (ADMET) and toxicity prediction by komputer assisted technology (TOPKAT) analyses, all geranylated analogues (3a–g) showed no hepatotoxicity effect and were biodegradable, which indicated that they could be potentially safe drugs for treating inflammation.

Purpose: The purpose of this paper is to evaluate the antioxidant activity and toxicity of Clinacanthus nutans leaves from three conventional extraction methods, i.e. maceration, Soxhlet and magnetic stirring.Design/methodology/approach: Total flavonoid content (TFC) and phenolic content (TPC) were determined using colorimetric method of aluminum chloride and Folin-Ciocalteu (FC) assay, respectively. Antioxidant property of C. nutans was evaluated using 2,2'-diphenyl-1-pierylhydrazyl (DPPH) free radical scavenging assay. Cytotoxic activity of C. nutans against brine shrimp was evaluated based on LC50 (lethality concentration) after 24 h exposure to the plant extract.Findings: The highest TPC of C. nutans was observed with Soxhlet extraction method (98.87 ± 10.43 mg of gallic acid equivalents (GAE/g) followed by maceration (68.77 ± 2.45 mg of GAE/g) and magnetic stirring (46.75 ± 2.45 mg of GAE/g). Interestingly, remarkable highest TFC was observed with magnetic stirring (568.90 ± 4.85 mg of rutin equivalent (RE)/g) followed by maceration (249.60 ± 2.79 mg of RE/g) and Soxhlet (174.8 ± 1.74 mg of RE/g). On the other hands, the extract obtained using maceration method showed the highest antioxidant activity (IC50: 14.18 mg/mL compared to ascorbic acid 144.36 µg/mL). Cytotoxicity of C. nutans from all extraction methods showed similar LC50 values with maceration (3.81 mg/mL), Soxhlet (2.61 mg/mL) and magnetic stirring (4.56 mg/mL), respectively.Originality/value: Both phenolic and flavonoids are responsible for the antioxidant activity, of C. nutans extracts. Based on Meyer's toxicity index, all extracts were nontoxic (LC50>1 mg/mL).