Biological activities evaluation of enantiopure isoxazolidine derivatives: in vitro, in vivo and in silico studies

A series of enantiopure isoxazolidines (3a–c) were synthesized by 1,3-dipolar cycloaddition between a (−)-menthone-derived nitrone and various terminal alkenes. The screened compounds were evaluated for their antioxidant activity by two in vitro antioxidant assays, including β-carotene/linoleic acid bleaching, and inhibition of lipid peroxidation (thiobarbituric acid reactive species, TBARS). The results revealed that compound 3b (EC50 = 0.55 ± 0.09 mM) was the most potent antioxidant as compared to the standard drug (EC50 = 2.73 ± 0.07 mM) using the TBARS assay. Furthermore, the antimicrobial activity was assessed using disc diffusion and microdilution methods. Among the synthesized compounds, 3c was found to be the most potent antimicrobial agent as compared to the standard drug. Subsequently, the acute toxicity study has also been carried out for the newly synthesized compounds and the experimental studies revealed that all compounds were safe up to 500 mg/kg and no death of animals were recorded. The cytotoxicity of these compounds was assessed by the MTT cell proliferation assay against the continuous human cell lines HeLa and compound 3c (GI50 = 46.2 ± 1.2 μM) appeared to be more active than compound 3a (GI50 = 200 ± 2.8 μM) and 3b (GI50 = 1400 ± 7.8 μM). Interestingly, all tested compounds displayed a good α-amylase inhibitory activity in competitive manner with IC50 values ranging between 23.7 and 64.35 μM when compared to the standard drug acarbose (IC50 = 282.12 μM). In addition, molecular docking studies were performed to understand the possible binding and the interaction of the most active compounds to the α-amylase pocket.info:eu-repo/semantics/publishedVersio

Rhaponticum acaule (L) DC essential oil: chemical composition, in vitro antioxidant and enzyme inhibition properties

Background: α-glucosidase is a therapeutic target for diabetes mellitus (DM) and α-glucosidase inhibitors play a vital role in the treatments for the disease. Furthermore, xanthine oxidase (XO) is a key enzyme that catalyzes hypoxanthine and xanthine to uric acid which at high levels can lead to hyperuricemia which is an important cause of gout. Pancreatic lipase (PL) secreted into the duodenum plays a key role in the digestion and absorption of fats. For its importance in lipid digestion, PL represents an attractive target for obesity prevention. Methods: The flowers essential oil of Rhaponticum acaule (L) DC (R. acaule) was characterized using gas chromatography-mass spectrometry (GC-MS). The antioxidant activities of R. acaule essential oil (RaEO) were also determined using 2,2’-azinobis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS), reducing power, phosphomolybdenum, and DNA nicking assays. The inhibitory power of RaEO against α-glucosidase, xanthine oxidase and pancreatic lipase was evaluated. Enzyme kinetic studies using Michaelis-Menten and the derived Lineweaver-Burk (LB) plots were performed to understand the possible mechanism of inhibition exercised by the components of this essential oil. Results: The result revealed the presence of 26 compounds (97.4%). The main constituents include germacrene D (49.2%), methyl eugenol (8.3%), (E)-β-ionone (6.2%), β-caryophyllene (5.7%), (E,E)-α-farnesene (4.2%), bicyclogermacrene (4.1%) and (Z)-α-bisabolene (3.7%). The kinetic inhibition study showed that the essential oil demonstrated a strong α-glucosidase inhibiton and it was a mixed inhibitor. On the other hand, our results evidenced that this oil exhibited important xanthine oxidase inhibitory effect, behaving as a non-competitive inhibitor. The essential oil inhibited the turkey pancreatic lipase, with maximum inhibition of 80% achieved at 2 mg/mL. Furthermore, the inhibition of turkey pancreatic lipase by RaEO was an irreversible one. Conclusion: The results revealed that the RaEO is a new promising potential source of antioxidant compounds, endowed with good practical applications for human health. Keywords: α-glucosidase, Antioxidant activity, Chemical composition, Pancreatic lipase inhibition, Rhaponticum acaule essential oil, Xanthine oxidase

Antioxidant, antimicrobial and phytotoxic activities of Rhaponticum acaule DC. essential oil

The in-vitro antioxidant activity of Rhaponticum acaule essential oil (RaEO) was evaluated using beta-carotene/linoleic acid bleaching, chelating activity, and lipid peroxidation inhibition (TBARS) assays. The antimicrobial activity of RaEO was assessed by disc diffusion and microdilution methods against 8 bacteria and 4 yeast. Finally, the allelopathic activity of RaEO on the seed germination and the shoot and root elongation of lettuce (Lactuca sativa L.) seedlings were investigated. According to our results, the RaEO exhibited significant antioxidant activity, similar to those of standards (BHT and ascorbic acid) with IC50 values of 0.042 and 0.045 mg/mL obtained by beta-carotene bleaching and TBARS assays, respectively. On the other hand, despite its interesting ferrous chelating activity, RaEO possesses moderate IC50 value (0.35 mg/mL) as compared with that of EDTA (0.015 mg/mL). RaEO exhibited a strong antimicrobial activity against all the tested microorganisms, with IZ, MIC and MBC values being in the range of 7.67 +/- 0.58 to 13.33 +/- 0.58 mm, 1.25 to 5.00 and 5.00 to 10.00 mg/mL, respectively. The results reveled also that RaEO inhibited the shoot and root growth of Lactuca sativa L. seedlings. Our data suggested that the RaEO had pharmaceutical benefits and could be used as a potential natural herbicide resource

Borano-nucleotides: new analogues to circumvent HIV-1 RT-mediated nucleoside drug-resistance

International audienceAlpha-boranophosphates suppress RT-mediated resistance when the catalytic rate of incorporation (kpol) of the analogue 5'-triphosphate is responsable for drug resistance, such as in the case of K65R mutant and ddNTPs, and Q151M toward AZTTP and ddNTPs. This suppression is also observed with BH3-d4T and BH3-3TC toward their clinically relevant mutants Q151M and M184V. Moreover, the presence of the borano (BH3-) group renders the incorporation of the analogue independent from amino-acid substitutions in RT. To our knowledge, this is the first example of rescue of polymerase activity by means of a nucleotide analogu

Chemical composition and biological activities of Eruca vesicaria subsp. longirostris essential oils

Context To date, there are no reports to validate the Tunisian traditional and folklore claims of Eruca vesicaria (L) Cav. subsp. longirostris (Brassicaceae) for the treatment of disease. Objective Investigation of the chemical composition antimicrobial and antioxidant activity of essential oils from Eruca longirostris leaves, stems, roots and fruits. Materials and methods The essential oils of E. longirostris from leaves, stems, roots and fruits were obtained after 4 h of hydrodistillation. Chemical compositions were determined using a combination of GC/FID and GC/MS. The in vitro antimicrobial activity of the volatile constituents of E. longirostris was performed in sterile 96-well microplates against three Gram-positive, four Gram-negative bacteria and one strain as yeast. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values were reported. Furthermore, the antioxidant activity was evaluated by DPPH and ABTS assays. Results The main compound for fruits, stems and roots was the erucin (96.6%, 85.3% and 83.7%, respectively), while β-elemene (35.7%), hexahydrofarnesylacetone (23.9%), (E)-β-damascone (15.4%), erucin (10.6%) and α-longipinene (9.6%) constituted the major compounds in the essential oil of the leaves. The experimental results showed that in all tests, essential oil of fruits showed the better antioxidant activity than the others. On the other hand, the oils of stems, fruits and roots showed significant antimicrobial activity with MIC values ranging from 0.125 to 0.31 mg/mL against Candida species, Gram-positive and Gram-negative bacteria, mainly Salmonella enterica. Conclusions The present results indicate that essential oils of E. longirostris can be used as a source of erucin

Phytochemical characterization, antioxidant, antimicrobial and pharmacological activities of Feijoa sellowiana leaves growing in Tunisia

In this study, headspace solid-phase microextraction coupled to GC–MS was applied to identify the volatile bioactive compounds in the leaves of Feijoa sellowiana growing in Tunisia. Thirty-one components were identified, representing 99.9% of the total volatiles. The major constituents were limonene (36.2%), β-caryophyllene (27.8%), aromadendrene (12.5%), and α-copaene (6.6%). Also, the F. sellowiana leaves extract (FSLE) was phytochemically characterized. Antioxidant activity was estimated by different in vitro assays, such as ABTS cation radicals scavenging, iron-chelating capability, ability to inhibit lipid peroxidation, superoxide inhibition and DNA protection assay. The antibacterial and antifungal activities of FSLE were also investigated by the disc diffusion and microdilution methods. In vitro inhibition of diabetes key enzymes (α-glucosidase and α-amylase) was evaluated. The study of kinetics inhibition showed that the FSLE demonstrated a strong inhibition of both α-glucosidase (IC50=8.0 ± 0.2 μg/ mL) and α-amylase (IC50=70.20 ± 0.8 μg/mL) in non-competitive manner. The acute toxicity of FSLE on Wistar rats at the doses of 200, 500 and 2000 mg/kg body weight (BW) was investigated. Our findings revealed that leaves extract at such doses as up to 2000 mg/kg did not cause any signs of toxicity or deaths in rats. Based on hematological and biochemical analyses of hepato-biliary and renal functions, we concluded that the FSLE is tolerated by rats. The analgesic effect of FSLE was assayed using the acetic acid writhing test in mice. At 100 mg/ kg, the FSLE showed a higher analgesic activity (88.08 ± 0.73%) than that of acetylsalicylic acid (ASL) (62.69 ± 0.26%) used as positive control

Wild Vitex agnus-castus L.: phytochemical characterization, acute toxicity, and bioactive properties

Wild Vitex agnus-castus (VAC) is a Mediterranean plant that is rich in bioactive metabolites. This study aimed to validate, for the first time, the beneficial use of VAC fruits and fruit decoctions (VFDs) through in vitro and in vivo trials. Forty-one volatile components were detected in VAC fruits, with 1,8-cineole (30.3%) comprising the majority. The antioxidant activity of VFD was measured by using different in vitro methods (EC50 of 0.16 mg/mL by β-carotene bleaching inhibition assay) and by measuring the DNA protection power. Using the disc diffusion assay, the antimicrobial activity of VFD was evaluated, and it exhibited a noticeable anticandidal activity. VFD did not cause any toxicity or mortality in rats treated with doses > 200 mg/kg. Using the acetic acid writhing test, the antinociceptive activity of VFD was measured. Our results showed that VFD at 200 mg/kg exhibited a higher analgesic activity (81.68%) than acetylsalicylic acid used as a positive control (74.35%). Its gastroprotective ability was assessed by HCl/ethanol-induced gastric lesions, which were remarkably inhibited (84.62%) by intraperitoneal administration of VFD. This work helps to validate the popular use of VAC to treat nociceptive, inflammatory, and gastric disorders and encourages researchers to further investigate the identification of pharmacological compounds from this species.ALIMNOVA UCM Research Group 951505Universidad Complutense de MadridDepto. de Nutrición y Ciencia de los AlimentosFac. de FarmaciaTRUEpu