Cycloartane-type triterpenoids from the leaves of Sandoricum koetjape and their efficacy on α-glucosidase inhibition activity.

The preliminary α-glucosidase inhibitory activity of the methanol extract of the leaves of Sandoricum koetjape Merr. exhibited promising results. The leaves was extracted with methanol to obtain the methanol extract that was continuedly partitioned with hexane and ethyl acetate. Those fractions were further purified by various chromatographic techniques. The isolation of the potent fractions furnished two new cycloartane-type triterpenoids (1 and 2) along with ten known compounds (3-12). Their chemical structures were unambiguously established by interpretation of NMR (1 D & 2 D) and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Furthermore, the configurations of two new compounds were determined by using NOESY spectrum as well as comparing their NMR data to the reference. These compounds were evaluated against α-glucosidase. All tested compounds revealed potent activity with IC50 value in the range of 2.17-49.2 µM compared to that of acarbose (IC50 100.6 µM). Compound 10 showed the lowest IC50 value. This compound was reported as a mixed-type inhibitor. Compound 3 possessed the second strong activity with an IC50 value of 14.0 µM and was further investigated on kinetic analysis which revealed as a mixed-type inhibitor with Ki and Ki' values of 59.1 and 155.2 µM, respectively.

The 8-bromobaicalein alleviated chikungunya-induced musculoskeletal inflammation and reduced the viral load in healthy adult mice.

Chikungunya virus is a re-emerging arbovirus that has caused epidemic outbreaks in recent decades. Patients in older age groups with high viral load and severe immunologic response during acute infection are likely to develop chronic arthritis and severe joint pain. Currently, no antiviral drug is available. Previous studies suggested that a flavone derivative, 8-bromobaicalein, was a potential dengue and Zika replication inhibitor in a cell-based system targeting flaviviral polymerase. Here we characterized that 8-bromobaicalein inhibited chikungunya virus replication with EC50 of 0.49 ± 0.11 µM in Vero cells. The molecular target predicted at viral nsP1 methyltransferase using molecular binding and fragment molecular orbital calculation. Additionally, oral administration of 250 mg/kg twice daily treatment alleviated chikungunya-induced musculoskeletal inflammation and reduced viral load in healthy adult mice. Pharmacokinetic analysis indicated that the 250 mg/kg administration maintained the compound level above EC99.9 for 12 h. Therefore, 8-bromobaicalein should be a potential candidate for further development as a pan-arboviral drug.

The 8-bromobaicalein inhibited the replication of dengue, and Zika viruses and targeted the dengue polymerase.

Dengue and Zika viruses are mosquito-borne flaviviruses burdening millions every year with hemorrhagic fever and neurological symptoms. Baicalein was previously reported as a potential anti-flaviviral candidate and halogenation of flavones and flavanones potentiated their antiviral efficacies. Here, we reported that a chemically modified 8-bromobaicalein effectively inhibited all dengue serotypes and Zika viruses at 0.66-0.88 micromolar in cell-based system. The compound bound to dengue serotype 2 conserved pocket and inhibited the dengue RdRp activity with 6.93 fold more than the original baicalein. Moreover, the compound was mildly toxic against infant and adult C57BL/6 mice despite administering continuously for 7 days. Therefore, the 8-bromobaicalein should be investigated further in pharmacokinetics and efficacy in an animal model.

A new series of chrysin derivatives as potent non-saccharide ⍺-glucosidase inhibitors.

Twenty-three chrysin derivatives were designed and synthesized by alkylation and bromination reactions. Their structures were confirmed by NMR and mass spectrometry, and their in vitro ⍺-glucosidase (AG) inhibitory activity was investigated. Chrysin derivatives except for 3a, 3b, 2q, and 2r, revealed better activity than the reference acarbose with moderate to very strong inhibition against AG. Notably, 2f, 2j, and 4 showed very strong and strong effects on AG ⍺-glucosidase inhibitory activity with IC50 values of 0.08, 3.47, and 2.97 µM, respectively. Simultaneously, enzyme kinetics study indicated that 2f was a competitive-type inhibitor, while 2j and 4 were mixed-type inhibitors.

Phytochemical and antioxidant activity evaluation of the bark of Tampoi ( Baccaurea macrocarpa).

Background: Tampoi ( Baccaurea macrocarpa) is a tropical rainforest plant that produces edible fruit and is native to Southeast Asia, especially East Kalimantan, Indonesia. Previous research showed that Tampoi potentially can be developed as a drug. It was reported that the extract of Tampoi fruit displayed antioxidant activity, which was correlated with its phenolic and flavonoid substances. There is no information about the antioxidant activity of other parts of this plant, such as the bark, which might also have this kind of activity. Therefore, the aim of this study was to evaluate the phytochemical, toxicity, and antioxidant activity of the bark of Tampoi. Methods : The bark of Tampoi was extracted with methanol and concentrated using rotary evaporator to obtain the methanol extract of the bark. Secondary metabolites of this extract was determined using phytochemical analysis. Afterward, the methanol extract was tested for its toxicity using brine shrimp lethality test and antioxidant activity using the 2,2-diphenyl-1-picrylhydrazyl method. Results: Phytochemical evaluation results showed that the methanol extract of bark of this plant contains several secondary metabolites including alkaloids, flavonoids, phenolics, steroids, and triterpenoids. The toxicity test displayed no toxic property due to a LC 50 value above 1000 ppm. For antioxidant activity, the result exhibited that the methanol extract of bark of this plant could be categorized as an active extract with IC 50 value of 11.15 ppm. Moreover, based on gas chromatography-mass spectrometer analysis, there are 37 isolated compounds from the bark, one of which is methylparaben, a phenolic predicted to act as an antioxidant. Conclusion : The results obtained in this research demonstrated that the bark of Tampoi ( B. macrocarpa) has potential as an antioxidant.

CBMG, a novel derivative of mansonone G suppresses adipocyte differentiation via suppression of PPARγ activity.

Mansorins and mansonones have been isolated from Mansonia gagei heartwoods, a traditional herbal medicine used to treat heart failure, and characterized to have anti-oxidant, anti-bacterial, anti-tumor, and anti-estrogenic activities. However, there is as yet no information on their effects on adipogenesis and lipid storage associated with heart disease. In this study, we investigated the effects of naturally occurring compounds on adipogenic differentiation and sought to develop more potent anti-adipogenic compound. We found that mansonone G (MG) suppressed adipocyte differentiation of 3T3-L1 cells, with a 40% decrease in lipid accumulation at 10 µM. MG derivatives including ether and ester analogues were then synthesized and assayed for their ability to suppress adipogenesis. A novel MG derivative, chlorobenzoyl MG (CBMG) most potently suppressed adipocyte differentiation with the decreased level of aP2 and adiponectin. Interestingly, CBMG treatment decreased the expression of CCAAT enhancer binding protein-α (C/EBPα) and peroxisome proliferator-activated receptor-γ (PPARγ). Further analysis confirmed that CBMG suppressed both the expression and activity of PPARγ, a master regulator of adipogenesis, and subsequently led to decreases in transcription of C/EBPα, aP2, and adiponectin in adipogenesis, thereby attenuating adipocyte differentiation. Our results suggest that a novel MG derivative, CBMG may have beneficial applications in the control of obesity through the suppression of PPARγ-induced adipocyte differentiation and lipid accumulation.

Allyl and prenyl ethers of mansonone G, new potential semisynthetic antibacterial agents.

Four natural 1,2-naphthoquinones: mansonones C, E, G, and H were isolated from the dichloromethane extract of Mansonia gagei Drumm. heartwoods. Mansonone G was further converted to eight ether and four ester analogues. The structures of mansonones and the analogues were well-confirmed by spectroscopic techniques. All compounds were evaluated for their antibacterial activity against Gram-positive and negative bacteria. Further modification of mansonone G furnished certain analogues displaying better activity than natural mansonones. Particularly, allyl and prenyl ethers of mansonone G exhibited better activity against Staphylococcus aureus with MIC sixty-four times better than their natural compound.