Enhanced synthesis of novel multisubstituted isoxazolidines as potential antimicrobial and antioxidant agents using zinc (II) catalyst, and in silico studies

Al-Adhreai, Arwa; ALSaeedy, Mohammed; Alrabie, Ali; Al-horaibi, Sultan A.; Al-Qadsy, Inas; Alezzy, Abdulmajeed  A.; Al-Odayni, Abdel-Basit; Saeed, Waseem Sharaf; Farooqui, Mazahar

doi:10.1016/j.molstruc.2023.136146

Cited by 3 publications

(3 citation statements)

References 29 publications

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“…1H NMR (CDCl 3 , 400 MHz) δppm: 0.64 (d, 3H, J = 6.4 Hz, CH 3 ); 0.78 (d, 3H, J = 6.8 Hz, CH 3 ); 0.79 (d, 3H, J = 6.4 Hz, CH 3 ); 0.82 (m, 1H); 1.07 (t, 1H, J = 12.4 Hz); 1.20 (t, 1H, J = 7.2 Hz); 1. 25…”

Section: General Procedures D For the Preparation Of Compounds 5a-gmentioning

confidence: 99%

“…1H NMR (CDCl 3 , 400 MHz) δppm: 0.65 (d, 3H, J = 6.4 Hz, CH 3 ); 0.80 (2d, 6H, J = 6.8 Hz, 2CH 3 ); 0.84-0.87 (m, 1H); 1.09 (t, 1H, J = 12.4 Hz); 1. 25…”

Section: General Procedures D For the Preparation Of Compounds 5a-gmentioning

confidence: 99%

“…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%

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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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Section: General Procedures D For the Preparation Of Compounds 5a-gmentioning

confidence: 99%

“…1H NMR (CDCl 3 , 400 MHz) δppm: 0.65 (d, 3H, J = 6.4 Hz, CH 3 ); 0.80 (2d, 6H, J = 6.8 Hz, 2CH 3 ); 0.84-0.87 (m, 1H); 1.09 (t, 1H, J = 12.4 Hz); 1. 25…”

Section: General Procedures D For the Preparation Of Compounds 5a-gmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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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Dual docking of some synthesized isoxazolidine derivatives against Cathepsin L and main protease as a novel treatment strategy for COVID-19

Al-Madhagi,

Al-Adhreai,

ALSaeedy

et al. 2024

Journal of Molecular Structure

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New 3-(Dibenzyloxyphosphoryl)isoxazolidine Conjugates of N1-Benzylated Quinazoline-2,4-diones as Potential Cytotoxic Agents against Cancer Cell Lines

Łysakowska,

Głowacka,

Honkisz-Orzechowska

et al. 2024

Molecules

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In this study, a new series of cis and trans 5-substituted-3-(dibenzyloxyphosphoryl)isoxazolidines 16a–g were synthesized by the 1,3-dipolar cycloaddition reaction of N-benzyl-C-(dibenzyloxyphosphoryl)nitrone and selected N1-allyl-N3-benzylquinazoline-2,4-diones. All the obtained trans-isoxazolidines 16a–g and the samples enriched in respective cis-isomers were evaluated for anticancer activity against three tumor cell lines. All the tested compounds exhibited high activity against the prostate cancer cell line (PC-3). Isoxazolidines trans-16a and trans-16b and diastereoisomeric mixtures of isoxazolidines enriched in cis-isomer using HPLC, namely cis-16a/trans-16a (97:3) and cis-16b/trans-16b (90:10), showed the highest antiproliferative properties towards the PC-3 cell line (IC50 = 9.84 ± 3.69–12.67 ± 3.45 μM). For the most active compounds, induction apoptosis tests and an evaluation of toxicity were conducted. Isoxazolidine trans-16b showed the highest induction of apoptosis. Moreover, the most active compounds turned out safe in vitro as none affected the cell viability in the HEK293, HepG2, and HSF cellular models at all the tested concentrations. The results indicated isoxazolidine trans-16b as a promising new lead structure in the search for effective anticancer drugs.

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Enhanced synthesis of novel multisubstituted isoxazolidines as potential antimicrobial and antioxidant agents using zinc (II) catalyst, and in silico studies

Cited by 3 publications

References 29 publications

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

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

Dual docking of some synthesized isoxazolidine derivatives against Cathepsin L and main protease as a novel treatment strategy for COVID-19

New 3-(Dibenzyloxyphosphoryl)isoxazolidine Conjugates of N1-Benzylated Quinazoline-2,4-diones as Potential Cytotoxic Agents against Cancer Cell Lines

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