Design and synthesis of novel enantiopure Bis(5-Isoxazolidine) derivatives: insights into their antioxidant and antimicrobial potential via in silico drug-likeness, pharmacokinetic, medicinal chemistry properties, and molecular docking studies

Alrabie, Ali; ALSaeedy, Mohammed; Alrabie, Ali; Al-Qadsy, Inas; Dawbaa, Sam; Alaizeri, ZabnAllah M.; Alhadlaq, Hisham A.; Al-Kubati, Abdulrahman; Ahamed, Maqusood; Farooqui, Mazahar

doi:10.1016/j.heliyon.2022.e09746

Cited by 16 publications

(3 citation statements)

References 25 publications

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“…Some of these compounds are known as antioxidant agents, according to the literature. For instance, AL-Adhreai et al [40] reported the antioxidant potential of isoxazolidine supported by in vitro, in silico and pharmacodynamic studies. In addition, N-propylacetamide found in B. ferruginea is used as an antiepileptic agent, but it anti-oxidant property is also reported [41].…”

Section: Resultsmentioning

confidence: 99%

Phytochemical composition, antioxidant and cytotoxicity of the aqueous extracts of Dracaena arborea andBridelia ferruginea: in vitro and in silico studies.

Deeh,

Kim,

Sathiyaseelan

et al. 2024

Preprint

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This study was undertaken to determine the phytochemical profile, antioxidant and cytotoxicity of the aqueous extracts of Dracaena arborea (DA) and Bridelia ferruginea (BF). The phytochemical composition, total phenolic (TP) and flavonoid (TF) contents of the extracts were determined by GC-MS, Folin Ciocalteu and AlCl3 methods, respectively. The antioxidant power was estimated using DPPH and ABTS+ radicals scavenging method, and cupric and ferric reducing capacity assay. The effect of extracts on hemolysis was also determined using red blood cells. Selected phytocompounds were docked against some oxidative stress (Keap1 and GST) and cytotoxicity (PARP10 and p90 RSK) proteins. The TP and TF content of BF was significantly (p < 0.001) higher than that of DA. The DPPH, ABTS+, cupric and ferric reducing activity of BF were significantly (p < 0.05 − 0.001) higher than those of DA. DA decreased the viability of PC3, NIH3T3 and BT474 cells in a dose-dependent manner, while BF tended to feed the cells. Drug-Likeness and toxicity prediction of selected compounds found in the plant extracts were within the acceptable standards, according to Lipinski’s rule. BF has the possibility to be exploited in the prevention/treatment of oxidative stress-related diseases, while DA could be a potential anticancer agent.

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Section: Resultsmentioning

confidence: 99%

Phytochemical composition, antioxidant and cytotoxicity of the aqueous extracts of Dracaena arborea andBridelia ferruginea: in vitro and in silico studies.

Deeh,

Kim,

Sathiyaseelan

et al. 2024

Preprint

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show abstract

“…The 2D structures of ligand and complexes were made using ChemDraw Professional 16.0. Next, the 3D structures of the ligand and complexes were prepared by MOE software (protonation, partial charges and energy minimization) [50,51].…”

Section: Molecular Docking Using Moementioning

confidence: 99%

Antimicrobial Activity of Novel Ni(II) and Zn(II) Complexes with (E)-2-((5-Bromothiazol-2-yl)imino)methyl)phenol Ligand: Synthesis, Characterization and Molecular Docking Studies

Al-Qadsy,

Saeed,

Al-Owais

et al. 2023

Antibiotics

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In order to address the challenges associated with antibiotic resistance by bacteria, two new complexes, Ni(II) and Zn(II), have been synthesized using the conventional method based on Schiff base ligand (E)-2-((5-bromothiazol-2-yl) imino) methyl) phenol. The Schiff base ligand (HL) was synthesized using salicylaldehyde and 5-(4-bromophenyl)thiazol-2-amine in both traditional and efficient, ecologically friendly, microwave-assisted procedures. The ligand and its complexes were evaluated by elemental analyses, FTIR spectroscopy, UV-Vis spectroscopy, nuclear magnetic resonance (NMR), thermogravimetric analysis (TGA) and magnetic susceptibility. The ligand and its complexes were tested for antibacterial activity against three Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Methicillin-resistant Staphylococcus aureus ATCC 43300 and Enterococcus faecalis ATCC 29212) and three Gram-negative bacteria (Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603). The findings demonstrate the potent activity of the ligand and its complexes against selective bacteria but the Ni(II) complex with MIC values ranging from 1.95 to 7.81 µg/mL outperformed all other compounds, including the widely used antibiotic Streptomycin. Furthermore, the docking study provided evidence supporting the validity of the antimicrobial results, since the Ni complex showed superior binding affinity against to E. coli NAD synthetase, which had a docking score (−7.61 kcal/mol).

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“…A recent study showed that compounds containing an isoxazolidine ring can be antidiabetic [ 11 , 20 ]. Additionally, some natural isoxazolidine derivatives are known for their diverse biological activities [ 21 , 22 , 23 ] ( Figure 1 ), such as anticancer [ 24 ], antibacterial [ 25 ], antifungal [ 26 ], and antioxidant [ 27 ] properties. Isoxazolidine analogs have also been used as a key intermediate to obtain natural compounds of high biological importance [ 28 , 29 , 30 ], such as 4-hydroxyisoleucine [ 31 ], a natural hypoglycemic agent.…”

Section: Introductionmentioning

confidence: 99%

In Silico Design, Synthesis, and Evaluation of Novel Enantiopure Isoxazolidines as Promising Dual Inhibitors of α-Amylase and α-Glucosidase

Alhawday,

Alminderej,

Ghannay

et al. 2024

Molecules

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Isoxazolidine derivatives were designed, synthesized, and characterized using different spectroscopic techniques and elemental analysis and then evaluated for their ability to inhibit both α-amylase and α-glucosidase enzymes to treat diabetes. All synthesized derivatives demonstrated a varying range of activity, with IC50 values ranging from 53.03 ± 0.106 to 232.8 ± 0.517 μM (α-amylase) and from 94.33 ± 0.282 to 258.7 ± 0.521 μM (α-glucosidase), revealing their high potency compared to the reference drug, acarbose (IC50 = 296.6 ± 0.825 µM and 780.4 ± 0.346 µM), respectively. Specifically, in vitro results revealed that compound 5d achieved the most inhibitory activity with IC50 values of 5.59-fold and 8.27-fold, respectively, toward both enzymes, followed by 5b. Kinetic studies revealed that compound 5d inhibits both enzymes in a competitive mode. Based on the structure–activity relationship (SAR) study, it was concluded that various substitution patterns of the substituent(s) influenced the inhibitory activities of both enzymes. The server pkCSM was used to predict the pharmacokinetics and drug-likeness properties for 5d, which afforded good oral bioavailability. Additionally, compound 5d was subjected to molecular docking to gain insights into its binding mode interactions with the target enzymes. Moreover, via molecular dynamics (MD) simulation analysis, it maintained stability throughout 100 ns. This suggests that 5d possesses the potential to simultaneously target both enzymes effectively, making it advantageous for the development of antidiabetic medications.

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Design and synthesis of novel enantiopure Bis(5-Isoxazolidine) derivatives: insights into their antioxidant and antimicrobial potential via in silico drug-likeness, pharmacokinetic, medicinal chemistry properties, and molecular docking studies

Cited by 16 publications

References 25 publications

Phytochemical composition, antioxidant and cytotoxicity of the aqueous extracts of Dracaena arborea andBridelia ferruginea: in vitro and in silico studies.

Phytochemical composition, antioxidant and cytotoxicity of the aqueous extracts of Dracaena arborea andBridelia ferruginea: in vitro and in silico studies.

Antimicrobial Activity of Novel Ni(II) and Zn(II) Complexes with (E)-2-((5-Bromothiazol-2-yl)imino)methyl)phenol Ligand: Synthesis, Characterization and Molecular Docking Studies

In Silico Design, Synthesis, and Evaluation of Novel Enantiopure Isoxazolidines as Promising Dual Inhibitors of α-Amylase and α-Glucosidase

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