To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with 5d being the most potent (MIC 3.95 mM against Staphylococcus aureus ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly 5c, exhibiting the strongest activity with IC₅₀ of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their α-amylase inhibitory effect, the examined analogues display a variable degree of α-amylase activity with IC₅₀ ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC₅₀ 1.19 ± 0.02 mM), with the most active compounds being 5d, followed by 5c and 5j, affording IC₅₀ of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.

In the current study the potential use of aqueous and methanolic extracts of Ephedra alata aerial parts as biological control agent against pathogenic bacteria and especially Staphylococcus aureus methicillin resistant isolated from auricular infections was evaluated. Chemical tests and spectrophotometric methods were used for screening and quantification of phytochemicals. The assessment of the antioxidant activity was accomplished by DPPH and ABTS radicals scavenging assays. Extracts were evaluated for their antibacterial efficacy by diffusion and microdilution methods. Biofilm inhibition was tested using XTT assay and the cytotoxicity of extracts was carried out on Vero cell line. The GC-FID analysis revealed that E. alata was rich in unsatured fatty acids. In addition, the aqueous extract had the highest flavonoid and protein contents (30.82 mg QE /g dry extract and 98.92 mg BSAE/g dry extract respectively). However, the methanolic extract had the highest phenolic, sugars and tannins. The antioxidant activity demonstrated that the aqueous extract exhibited the strong potency (IC50 ranged between 0.001 and 0.002 mg/mL).

Three-component cascade reactions of (E)-3-arylidene-1-methyl-pyrrolidine-2,5-diones, L-valine and various isatin derivatives are described. A series of 17 spiropyrrolidine derivatives with wide structural complexity and diversity have been thus obtained in moderate to excellent yields under mild reaction conditions. The structure and stereochemistry of these N-heterocyclic cycloadducts has been established by spectroscopic techniques and unambiguously confirmed by a single-crystal X-ray diffraction analysis performed on one derivative. UV-visible spectra have been recorded for all new compounds. Furthermore, the synthesized N-heterocyclic compounds have been screened for their in vitro antibacterial and antifungal activities. Several derivatives exhibited moderate to good activities, comparable to those of the known standard drugs Amphotericin B and Tetracycline. Structural activity relationships (SARs) and molecular docking of the most promising derivatives into the binding sites of glucosamine 6-phosphate synthase (GlcN6P) and methionyl-trna-synthetase (1PFV) were also established. Furthermore, pharmacokinetic studies indicate that the heterocycles exhibit acceptable predictive ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties and good drug ability.

In a sustained search for novel potential drug candidates with multispectrum therapeutic application, a series of novel spirooxindoles was designed and synthesized via regioselective three-component reaction between isatin derivatives, 2-phenylglycine and diverse arylidene-imidazolidine-2,4-diones (Hydantoins). The suggested stereochemistry was ascertained by an X-ray diffraction study and NMR spectroscopy. The resulting tetracyclic heterocycles were screened for their in vitro and in vivo anti-inflammatory and analgesic activity and for their in vitro antimicrobial potency. In vitro antibacterial screening revealed that several derivatives exhibited remarkable growth inhibition against different targeted microorganisms. All tested compounds showed excellent activity against the Micrococccus luteus strain (93.75 µg/mL ≤ MIC ≤ 375 µg/mL) as compared to the reference drug tetracycline (MIC = 500 µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and 4l showed significant inhibitory activity with IC₅₀ = 1.09 mg/mL and IC₅₀ = 1.01 mg/mL, respectively, more potent than the parent drug, diclofenac sodium (IC₅₀ = 1.19 mg/mL). In addition, in vivo evaluation of anti-inflammatory and analgesic activity of these spirooxindoles were assessed through carrageenan-induced paw edema and acetic acid-induced writhing assays, respectively, revealing promising results. In silico molecular docking and predictive ADMET studies for the more active spirocompounds were also carried out.

This study aimed to investigate the in vitro properties of lactic acid bacteria isolated from colostrum samples of goat, sheep and cow. Four isolates of lactic acid bacteria identified through 16S rDNA sequencing were screened for probiotic potential including their enzymatic activities (hemolytic, DNase activity, API ZYM profiling and tolerance to the gastrointestinal conditions), their antimicrobial activities, their adhesion properties through biofilm formation capacity, auto-aggregation and co-aggregation with pathogens bacteria and hydrophobicity. They were also tested for their antibiotic susceptibility and antioxidant power. All the strains (ADG1b Lactobacillus gasseri, ZPana Lactiplantibacillus plantarum, S2ana Enterococcus hirae and ZGana Lactobacillus gasseri) demonstrated probiotic properties and they could resist different gastrointestinal conditions. They displayed good antimicrobial activities. Furthermore, they had high antioxidant power, although strain dependent. The results of this study showed that L. gasseri (ADG1b) is the most promising probiotic.

Globularia alypum L. (GA) is a Mediterranean plant of the Globulariaceae family which is widely used in traditional Tunisian medicine. The main goal of this study was to evaluate the phytochemical composition, antioxidant, antibacterial, and antibiofilm activities, and the antiproliferative potential of different extracts of this plant. The identification and the quantification of the different constituents of extracts were determined using gas chromatography–mass spectrometry (GC-MS). The antioxidant activities were evaluated using spectrophotometric methods and chemical tests. The antiproliferative study was based on the use of colorectal cancer SW620 cells, including an antibacterial assessment with the microdilution method and analysis of the antibiofilm effects via the crystal violet assay. All extracts presented several components, mainly sesquiterpenes, hydrocarbon, and oxygenated monoterpenes. The results revealed that the maceration extract had the most important antioxidant effect (IC₅₀ = 0.04 and 0.15 mg/mL), followed by the sonication extract (IC₅₀ = 0.18 and 0.28 mg/mL). However, the sonication extract demonstrated significant antiproliferative (IC₅₀ = 20 µg/mL), antibacterial (MIC = 6.25 mg/mLand MBC > 25 mg/mL), and antibiofilm (35.78% at 25 mg/mL) properties against S. aureus. The results achieved confirm the important role of this plant as a source of therapeutic activities.