Structure-based drug design, molecular dynamics simulation, ADMET, and quantum chemical studies of some thiazolinones targeting influenza neuraminidase

Abdullahi, Mustapha; Uzairu, Adamu; Shallangwa, Gideon Adamu; Mamza, Paul Andrew; Ibrahim, Muhammad; Ahmad, Iqrar; Patel, Harun

doi:10.1080/07391102.2023.2208225

Cited by 9 publications

(2 citation statements)

References 92 publications

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“…The methodology followed in this study for modeling, using the α-glucosidase enzyme (PDB code: 3W37) and the α-amylase enzyme (PDB code: 2QV4), was similar to that described previously [ 59 , 60 , 61 , 62 ]. The protein structure was created and optimized using the Schrödinger software (Schrodinger, LLC, New York, USA, 2008) package’s protein production wizard.…”

Section: Methodsmentioning

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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Section: Methodsmentioning

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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show abstract

“…The OPLS3e force field was employed, and the SPC solvation model was utilized for solvation effects. The simulation parameters and experimental details were followed exactly as described in previous studies 46 , 47 . The duration of the MD simulation was 100 ns, and trajectory snapshots were captured at 100 ps intervals for analysis.…”

Section: Methodsmentioning

confidence: 99%

LC–MS profiling, in vitro and in silico C-ABL kinase inhibitory approach to identify potential anticancer agents from Dalbergia sissoo leaves

Naik,

Kanjariya,

Parveen

et al. 2024

Sci Rep

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Belonging to the Fabaceae family, Dalbergia sissoo, a versatile plant, has gained prominence for its potent medicinal attributes, especially antipyretic, anti-inflammatory, and cardioprotective properties, as well as the use of its leaf juice in cancer treatment. Despite these recognized applications by natives and tribals, comprehensive insight into its biological activities and chemical composition remains limited. This study aimed to explore the cytotoxic potential of sequentially extracted leaf extracts from Dalbergia sissoo using various solvents, aiming to unveil the array of phytochemicals through LC–MS profiling. Among the extracts evaluated, the extract employing methanol:water extracting media (HN-2) appeared with the most remarkable results in both phytochemical diversity and biological activity. Furthermore, in vitro results of HN-2's in vitro anticancer efficacy were confirmed through in silico molecular docking and molecular dynamics simulation. These analyses demonstrated its ability to inhibit C-ABL kinase within leukemia K562 cells, directing that Dalbergia sissoo leaves serve as a bioactive agent reservoir. Consequently, this suggests that the Dalbergia sissoo plant is a potential source of bioactive compounds that can be used as a precursor for developing new cancer inhibitors, mainly targeting leukemia.

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Development of novel thiazole-based hybrids as DNA gyrase inhibitors: design, synthesis, in silico and in vitro antibacterial evaluation

Vaghasiya,

Mendapara,

Ahmad

et al. 2024

J IRAN CHEM SOC

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Structure-based drug design, molecular dynamics simulation, ADMET, and quantum chemical studies of some thiazolinones targeting influenza neuraminidase

Cited by 9 publications

References 92 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

LC–MS profiling, in vitro and in silico C-ABL kinase inhibitory approach to identify potential anticancer agents from Dalbergia sissoo leaves

Development of novel thiazole-based hybrids as DNA gyrase inhibitors: design, synthesis, in silico and in vitro antibacterial evaluation

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