A novel role of Nano selenium and sildenafil on streptozotocin-induced diabetic nephropathy in rats by modulation of inflammatory, oxidative, and apoptotic pathways

El-Azab, Mona F.; Al‐Karmalawy, Ahmed A.; Antar, Samar A.; Hanna, Pierre Abi; Tawfik, Karim M.; Hazem, Reem M.

doi:10.1016/j.lfs.2022.120691

Cited by 27 publications

(19 citation statements)

References 90 publications

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“…Then, energy minimization was performed, followed by partial charge automatic calculation using the CHARMM27 force field [ 54 , 55 , 56 , 57 ]. Ultimately, they were imported into a single database along with the native co-crystallized O6K ligand and saved (MDB file) prior to the docking process within the target SARS-CoV-2 M pro pocket, as described earlier [ 58 , 59 , 60 , 61 ].…”

Section: Methodsmentioning

confidence: 99%

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Elmaaty

Eldehna

Khattab

et al. 2022

IJMS

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In this article, 34 anticoagulant drugs were screened in silico against the main protease (Mpro) of SARS-CoV-2 using molecular docking tools. Idraparinux, fondaparinux, eptifibatide, heparin, and ticagrelor demonstrated the highest binding affinities towards SARS-CoV-2 Mpro. A molecular dynamics study at 200 ns was also carried out for the most promising anticoagulants to provide insights into the dynamic and thermodynamic properties of promising compounds. Moreover, a quantum mechanical study was also conducted which helped us to attest to some of the molecular docking and dynamics findings. A biological evaluation (in vitro) of the most promising compounds was also performed by carrying out the MTT cytotoxicity assay and the crystal violet assay in order to assess inhibitory concentration 50 (IC50). It is worth noting that ticagrelor displayed the highest intrinsic potential for the inhibition of SARS-CoV-2 with an IC50 value of 5.60 µM and a safety index of 25.33. In addition, fondaparinux sodium and dabigatran showed promising inhibitory activities with IC50 values of 8.60 and 9.40 µM, respectively, and demonstrated safety indexes of 17.60 and 15.10, respectively. Moreover, the inhibitory potential of the SARS-CoV-2 Mpro enzyme was investigated by utilizing the SARS-CoV-2 Mpro assay and using tipranavir as a reference standard. Interestingly, promising SARS-CoV-2 Mpro inhibitory potential was attained for fondaparinux sodium with an IC50 value of 2.36 µM, surpassing the reference tipranavir (IC50 = 7.38 µM) by more than three-fold. Furthermore, highly eligible SARS-CoV-2 Mpro inhibitory potential was attained for dabigatran with an IC50 value of 10.59 µM. Finally, an SAR was discussed, counting on the findings of both in vitro and in silico approaches.

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Section: Methodsmentioning

confidence: 99%

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Elmaaty

Eldehna

Khattab

et al. 2022

IJMS

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“…Then, the chloroacetylated derivatives were condensed with the appropriate anilines in the presence of phosphorus This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2022 oxychloride to generate the required intermediates (1-5) in good yields. On the other hand, the intermediate hydroxychalcones (6)(7)(8)(9)(10)(11)(12) were obtained by condensation of p-hydroxyacetophenone and the appropriate benzaldehydes in ethanol in the presence of thionyl chloride at room temperature following reported procedures in good yields. 67 For the synthesis of the target compounds (13-43), the Williamson reaction was used.…”

Section: Chemistrymentioning

confidence: 99%

“…Apoptosis, or programmed cell death, is an important process required to maintain normal tissue development and homeostasis. 11,12 Induction of apoptosis is one of the main strategies that have been successfully approved in cancer treatment. [13][14][15] Apoptosis could be induced by the modulation of specific regulatory proteins such as caspase-3, caspase-9, BAX, and BCL-2.…”

Section: Introductionmentioning

confidence: 99%

Design and synthesis of novel quinazolinone–chalcone hybrids as potential apoptotic candidates targeting caspase-3 and PARP-1:in vitro, molecular docking, and SAR studies

et al. 2022

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“…[37][38][39][40][41][42] In preclinical studies, daily treatment of diabetic rats with sildenafil resulted in improvement in renal function and reduction in levels of markers of oxidative stress such as malondialdehyde and inhibition of pro-inflammatory cytokines. 43,44 Sildenafil appeared to have a modulatory effect on the pro-inflammatory high-mobility group box 1 (HMGB1)/nuclear factor-kappa b (NF-κB) pathway. 44 Concurrently, PDE5 inhibition demonstrated glucose lowering effects, likely through upregulating cGMP levels and thus improving insulin sensitivity.…”

Section: Antioxidant and Anti-apoptotic Cellular Effects Of Pde5imentioning

confidence: 99%

The efficacy of PDE5 inhibitors in diabetic patients

Święcicka

2022

Andrology

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Background: Phosphodiesterase 5 inhibitors (PDE5i), since their introduction in the late 1990s, have proven their efficacy in treating several conditions, predominantly pulmonary hypertension and erectile dysfunction where they remain the first-line therapeutic option. However, in the recent years, growing evidence from both animal and human studies has emerged to suggest the additional benefits of PDE5i in cardiovascular and metabolic disorders. This is of specific interest to the diabetes population where prevalent cardiovascular disease and metabolic dysregulation significantly contribute to the increased morbidity and mortality. Objectives:To examine the available data on the non-standard, pleiotropic effects of PDE5i in patients with diabetes mellitus. Materials and methods:The review of the published background research, preclinical studies and clinical trials. Results:In human studies, PDE5 inhibition appeared to be associated with reduced cardiovascular mortality and overall improved clinical outcomes in those with established cardiovascular disease. PDE5i were also consistently found to reduce albuminuria in subjects with diabetic nephropathy. Furthermore, animal data suggest a plausible effect of this group of medication on sensory function and neuropathic symptoms in diabetic neuropathy as well as improved wound healing. A decrease in insulin resistance and augmentation of beta cell function seen in preclinical studies has not been consistently demonstrated in human trials. Discussion and conclusion:In animal models, PDE5 inhibition appears to decrease oxidative stress and reduce some of the micro-and macrovascular complications associated with diabetes. However, data from human trials are limited and largely inconsistent, highlighting the need for adequately powered, randomised-controlled trials in diabetic cohorts in order to fully assess the benefits of PDE5i in this group of patients.

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A novel role of Nano selenium and sildenafil on streptozotocin-induced diabetic nephropathy in rats by modulation of inflammatory, oxidative, and apoptotic pathways

Cited by 27 publications

References 90 publications

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Anticoagulants as Potential SARS-CoV-2 Mpro Inhibitors for COVID-19 Patients: In Vitro, Molecular Docking, Molecular Dynamics, DFT, and SAR Studies

Design and synthesis of novel quinazolinone–chalcone hybrids as potential apoptotic candidates targeting caspase-3 and PARP-1:in vitro, molecular docking, and SAR studies

The efficacy of PDE5 inhibitors in diabetic patients

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