Chemistry & Biodiversity最新文献

Diabetes mellitus (DM) is a metabolic condition that is a profound health concern across the globe due to its contribution to the increased mortality rate. It affects millions of people around the world and is associated with severe complications among people diagnosed with it. Herein, we report the synthesis of benzylidenehydrazine derivatives as well as their evaluation as α-glucosidase and α-amylase inhibitors including their antioxidant testing. Generally, all the synthesized derivatives were more potent inhibitors of α-amylase than of α-glucosidase. Specifically, 2,4 fluoro substituted analogue 9 (IC50 =116.19 µM) emerged as the strongest α-amylase inhibitor with ~5-fold superior activity in comparison to the standard drug, acarbose (IC50 = 600 µM). Compounds 18 (IC50 = 240.59) and 19 (IC50 = 198.32 µM) displayed the strongest NO scavenging activity compared to Trolox (IC50 = 272.36 µM). In addition, the enzyme kinetic studies indicated that compound 9 acts as a non-competitive inhibitor of α-amylase. Finally, density functional theory and molecular docking studies for compound 9 were conducted to explore its structural and electronic properties as well as to determine protein-ligand interactions, respectively to decipher its observed activity.

Snakebite envenomation remains a significant medical challenge, particularly in tropical and subtropical regions. The present study investigates the inhibitory potential of Zingiber officinale (ginger) and its bioactive compounds against Naja nigricollis venom using in silico approaches and animal models. No protection was observed in the in vivo studies but the extract of the plant was able to prolong the time of death with mean survival time ranging from 2.01 - 2.83 hours. In terms of the in vitro studies, the extract was able to significantly (p<0.05) detoxify the N. nigricollis venom by 80 % at the graded doses; standard antisnake venom (ASV) offered 100 % protection to mice. Molecular docking analysis revealed strong binding affinities between the bioactive compounds and the PLA2 enzyme, indicating potential inhibitory effects. The stability and dynamics of the protein-ligand complexes were further validated through molecular dynamics (MD) simulations, which confirmed the persistence of these interactions over time. In conclusion, the findings suggest that the bioactive compounds from Z. officinale could serve as promising inhibitors of PLA2, providing a foundation for the development of novel snakebite envenomation therapies.

Five new secoiridoids, gentianopsins A-E (1-5), along with two known analogues (6 and 7) were isolated from the whole plants of the medicinal herb Gentianopsis barbata. Their structures were elucidated by a comparison of extensive spectroscopic analysis (1D and 2D NMR, and HRMS) and quantum chemical calculations. Gentianopsins A (1) and B (2) represented two unusual skeletons of trihomo-secoiridoids. Anti-inflammatory activity of these isolates was evaluated via suppressing the secretion of cytokines TNF-α and IL-6 in LPS-induced macrophages RAW264.7. Significant inhibitory activity was observed for compounds 3 and 7 on IL-6 secretion with IC50 values of 10.22 and 13.30 μM, respectively.

Melatonin (MLT) is a natural indolic hormone and its antioxidant activity has been reported through various mechanisms. MLT interacts with the estrogen signaling pathway by inhibiting aromatase enzyme, and it has been suggested that these new compounds may have endocrine-related adverse effects due to their selective estrogen modulator activity. In this study, we investigated the aromatase inhibitory and estrogen receptor agonist/antagonist effects as well as possible antioxidant activity of MLT analogue 5-floro indole derivatives for being potential drug candidates in the prevention and treatment of oxidative stress related diseases. Among the 34 compounds tested, three compounds showed antioxidant effect through radical scavenging activity and reducing the formation of intracellular reactive oxygen species.  They also showed varying potencies of antiestrogenic and/or aromatase inhibitory activity which should be considered as a potential untargeted effect of MLT and its analogues.

This study explores new anti-inflammatory agents by synthesizing pyrazoline-pyridine hybrids with N-butylsulfonated covalent organic framework (COF-SO3H) as a recyclable catalyst, achieving excellent yields in just one minute. The protocol was successfully scaled up to a multi-gram scale, highlighting its robustness and efficiency, and it operates without the need for column chromatography. Among the synthesized hybrids, compound 5d, a pyrazoline-pyridine hybrid bearing an indole moiety, emerged as a potent anti-inflammatory and antioxidant agent. It effectively inhibited PDE4B activation with an IC50 value of 99.38 nM, without adversely affecting HEK cells. Compound 5d demonstrated its dual activity by significantly reducing ROS production and restoring mitochondrial health in LPS-stimulated A549 and HEK cells, while also downregulating IL-1β and NF-ĸB/p65 expression in LPS-stimulated A549 cells. In silico studies confirmed compound 5d's strong binding to PDE4B, with stable RMSD and RMSF values, indicating its potential as a stable and effective PDE4B inhibitor. The compound exhibited favorable physicochemical properties, met drug-likeness criteria, and showed low toxicity as predicted in silico. These findings suggest that compound 5d has significant potential as a therapeutic agent for inflammatory diseases due to its dual anti-inflammatory and antioxidant activities.

Macroporous resin was used to enrich flavonoids in the ethyl acetate extract of Artemisia Selengensis Turcz. Based on a single factor experiment, the enrichment process was optimized using the response surface method. The optimal parameters of the enrichment process were a sample concentration of 0.3 mg/mL, a loading rate of 1 mL/min, an elution flow rate of 2 mL/min, and a total flavonoid content of 155.38 ± 0.97 mg/g. The flavonoids enriched by AB-8 macroporous resin demonstrated significant scavenging activities against DPPH, ABTS+, and hydroxyl free radicals, and also exhibited certain inhibitory effects on α-amylase and α-glucosidase. Among them, the scavenging ability of the flavonoids enriched by AB-8 macroporous resin on hydroxyl free radical (IC50 = 30.31 ± 1.92 μg/mL) was the closest to Vc, and the inhibitory effect on α-glucosidase (IC50 = 16.19 ± 1.35 μg/mL) was the best. These findings confirmed the potential of Artemisia Selengensis Turcz. is a natural antioxidant and hypoglycemic drug.

Aglanoideas A-C (1-3), three undescribed sesquiterpenes and eleven known compounds (4-14) were isolated from the leaves of Aglaia elaeagnoidea. Their structures including absolute configurations were characterized by using IR, HR-ESI-MS, NMR, and experimental and calculating ECD methods. Compounds 3-5 and 7 showed moderate nitric oxide inhibitory activity with IC50 value ranging from 53.7 to 72.5 µM.

A library of new thiazole linked tetrahydropyridines (6a-q) synthesized and screened for their invitro anticancer activity against human breast adeno carcinoma cell viz. MCF-7 and MDA-MB-231. The two compounds 6d containing -F and -Cl functions in para and meta position of phenyl ring (9.94 ± 1.02µM, 9.78 ± 1.08µM) and 6e with -Cl and -NH2 functions on pyridine ring (9.72 ± 0.91 µM,9.54 ± 0.95µM) demonstrated outstanding activity against both the cell lines when compared to Doxorubicin. The benzofuran analogue 6o presented good activity with an IC50 value of 12.19 ± 1.03µM (MCF-7) and 12.22 ± 1.07µM (MDA-MB-231). The molecular docking study of potent molecule 6e against crystal structure of breast tumor kinase presented promising docking score and binding interactions. Predicted pharmacokinetics properties of compounds 6a-q and presented boiled diagram of compounds 6d and 6e implied favourable drug-likeness properties.

Piper tuberculatum, traditionally known as 'pimenta-d'arda,' 'pimenta-longa,' or 'pimenta de macaco,' has been used in Brazilian folk medicine to treat inflammatory symptoms, It is used for its sedative effects in pain relief. Considering this species' significant essential oil content, the present study aimed to evaluate the anti-edematogenic and anti-inflammatory effects of the essential oil Piper tuberculatum (EOPT) in vivo. To this end, Swiss mice (Mus musculus) of both sexes were treated orally with the EOPT at 50, 100, and 250 mg/Kg. The rotarod and open field evaluated the potential activity in the central nervous system. At the same time, formalin and abdominal writhing tests were carried out to perform the pharmacological screening of the essential oil. Next, the anti-edematogenic effect was assessed using paw edema models induced by carrageenan, dextran, histamine, and arachidonic acid. The anti-inflammatory activity was then characterized in peritonitis (acute) and granuloma (chronic) models.  All the EOPT doses (50, 100, and 250 mg/kg) had analgesic effects associated with anti-inflammatory mechanisms in screening models. Accordingly, the treatment (EOPT 100 mg/Kg) inhibited the inflammatory process in acute and chronic models. In conclusion, EOPT has analgesic, antiedematogenic, and anti-inflammatory effects, highlighting its potential use in developing anti-inflammatory drugs.

Ethyl acetate extract of the cultures of the soil-derived filamentous fungus, Aspergillus variecolor SDG strain from Nallamala forest resulted in the isolation of extremely rare sesterterpenoids, stellatic acid (1) and andilesin C (2). We report a thorough chemical characterization of these compounds using various spectroscopic techniques and evaluation of their in vitro preclinical therapeutic potential. Stellatic acid exhibits potent antioxidant activity with an IC50 of 38 µg/mL and significant anticancer activity against HeLa, HepG2, MCF7, and A549 cancer cell lines with an IC50 of 7-12 µM. On the other hand, andilesin C displayed moderate cytotoxicity against DU145 and B16F10 cancer cell lines but lacked antioxidant activity. Furthermore, the potential hypoglycemic property of stellatic acid was evaluated by measuring its inhibitory effect against α-glucosidase. It exhibited tenfold potency against yeast  α-glucosidase (IC50 101.73 µg/mL) than mammalian α-glucosidase (IC50 1000.00 µg/mL). Docking studies were also performed to suggest the interaction mode of stellatic acid in the α-glucosidase enzyme active site. Notably, yeast α-glucosidase shows a higher affinity towards stellatic acid than mammalian α-glucosidase (3TOP). Thus, the in vitro preclinical study of stellatic acid suggests its potential efficacy in therapeutic drug development.