Optimizing the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach

Chaudhari, Bhagyashri Vijay; Patel, Harun; Snehal, Thakar; Ahmad, Iqrar; Bansode, Deepali A.

doi:10.1007/s40203-022-00125-1

Cited by 35 publications

(9 citation statements)

References 43 publications

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“…The antibacterial, antifungal, and antioxidant properties of the macromolecules were tested against S. aureus TyrRS (PDB ID: 1JIJ), S. aureus DNA gyrase (PDB ID: 2XCT), human peroxiredoxin 5 (PDB ID: 1HD2), C. albicans Sap 1 (PDB ID: 2QZW), MLK4 kinase domain (PDB ID: 4UYA), human kinesin (PDB ID: 4BBG), and BRCT protein (PDB ID: 1JNX) key enzymes. The protein preparation wizard panel, which adds hydrogen atoms, removes crystallographic water molecules, and converts seleno-methionine to methionine in the proper ionization state in the physiological environment, was used to prepare the retrieved protein structure [ 40 , 41 ]. To achieve low 3D structures with appropriate chiralities, the identified phyto-constituents were prepared using the LigPrep panel, which generates each ligand structure’s ionization state at a physiological pH of (7.2 ± 0.2).…”

Section: Methodsmentioning

confidence: 99%

Thymus musilii Velen. Methanolic Extract: In Vitro and In Silico Screening of Its Antimicrobial, Antioxidant, Anti-Quorum Sensing, Antibiofilm, and Anticancer Activities

Noumi

Ahmad²,

Bouali

et al. 2022

Life

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Thymus musilii Velen. is a rare plant species cultivated in the Ha’il region (Saudi Arabia) under greenhouse conditions. In this work, we described, for the first time, the phytochemical composition, antimicrobial, antioxidant, anti-quorum sensing, and anticancer activities of T. musilii methanolic extract using both experimental and computational approaches. The obtained results showed the identification of eight small-like peptides and eighteen phyto-compounds by using high-resolution liquid chromatography–mass spectrometry (HR-LCMS) dominated mainly by compounds belonging to isoprenoid, fatty acyl, flavonoid, and alkaloid classes. The tested extracts exhibited high antifungal and antibacterial activity with the mean diameter of growth inhibition zones ranging from 12.33 ± 0.57 mm (Pseudomonas aeruginosa ATCC 27853) to 29.33 ± 1.15 mm (Candida albicans ATCC 10231). Low minimal inhibitory concentrations were recorded for the tested micro-organisms ranging from 0.781 mg/mL to 12.5 mg/mL. While higher doses were necessary to completely kill all tested bacterial and fungal strains. Thyme extract was able to scavenge DPPH•, ABTS•+, β-carotene, and FRAP free radicals, and the IC50 values were 0.077 ± 0.0015 mg/mL, 0.040 ± 0.011 mg/mL, 0.287 ± 0.012 mg/mL, and 0.106 ± 0.007 mg/mL, respectively. The highest percentage of swarming and swimming inhibition was recorded at 100 µg/mL with 39.73 ± 1.5% and 25.18 ± 1%, respectively. The highest percentage of biofilm inhibition was recorded at 10 mg/mL for S. typhimurium ATCC 14028 (53.96 ± 4.21%) and L. monocytogenes ATCC 7644 (49.54 ± 4.5 mg/mL). The in silico docking study revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of T. musilii are thermodynamically feasible, notably, such as those of the tripeptides (Asn-Met-His, His-Cys-Asn, and Phe-His-Gln), isoprenoids (10-Hydroxyloganin), and diterpene glycosides (4-Ketoretinoic acid glucuronide).

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Section: Methodsmentioning

confidence: 99%

Thymus musilii Velen. Methanolic Extract: In Vitro and In Silico Screening of Its Antimicrobial, Antioxidant, Anti-Quorum Sensing, Antibiofilm, and Anticancer Activities

Noumi

Ahmad²,

Bouali

et al. 2022

Life

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“…However, RMSF variation was noticeable due to loop segments on 2'O methyltransferase. Since loop regions often contain unstructured portions of the protein that fluctuate more than secondary structural components (e.g., alpha helices and beta strands) [ 65 ]. Gly86, Arg84, and Ser56 formed H bonds within CHEMBL376820-2'O methyltransferase complex.…”

Section: Discussionmentioning

confidence: 99%

A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery

et al. 2022

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Dengue fever is a mosquito-borne disease that claims the lives of millions of people around the world. A number of factors like disease’s non-specific symptoms, increased viral mutation, growing antiviral drug resistance due to reduced susceptibility, unavailability of an effective vaccine for dengue, weak immunity against the virus, and many more are involved. Dengue belongs to the Flaviviridae family of viruses. The two species of the vector transmitting dengue are Aedes aegypti and Aedes albopictus , with the former one being dominant. Serotypes 2 of dengue fever are spread to the human body and cause severe illness. Recently, dengue has imposed an aggressive effect synergistically with the COVID-19 pandemic. As a result, we concentrated our efforts on finding a potential therapeutic. For this, we chose natural compounds to fight dengue fever, which is currently regarded as successful among many drug therapies. Following this, we started the in silico experiment with 922 plant extracts as lead compounds to fight serotype 2. In this study, we used SwissADME for analyzing ligand drug-likeness, pkCSM for designing an ADMET profile, Autodock vina 4.2 and Swissdock tools for molecular docking, and finally Desmond for molecular dynamics simulation. Ultimately 45 were found effective against the 2'O methyltransferase protein of serotype 2. CHEMBL376820 was found as possible therapeutic candidates for inhibiting methyltransferase protein in this thorough analysis. Nevertheless, more in vitro and in vivo research are required to substantiate their potential therapeutic efficacy. Supplementary Information The online version contains supplementary material available at 10.1007/s12033-022-00582-1.

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“…It is anticipated that the lesser RMSD value during the simulation reveals that the protein–ligand complex is more stable. In contrast, the higher RMSD value indicates the protein–ligand complex is less stable [ 111 , 112 , 113 ]. The overall RMSD revealed that fluctuations in the range of 1.6 Å to 2.8 Å were within the standard range (1–3 Å) of RMSD, indicating that the protein–ligand complex is stable.…”

Section: Discussionmentioning

confidence: 99%

Phytochemical Analysis, Antioxidant, and Antimicrobial Activities of Ducrosia flabellifolia: A Combined Experimental and Computational Approaches

Snoussi

Ahmad²,

Aljohani³

et al. 2022

Antioxidants

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Ducrosia flabellifolia Boiss. is a rare desert plant known to be a promising source of bioactive compounds. In this paper, we report for the first time the phytochemical composition and biological activities of D. flabellifolia hydroalcoholic extract by using liquid chromatography–electrospray tandem mass spectrometry (ESI-MS/MS) technique. The results obtained showed the richness of the tested extract in phenols, tannins, and flavonoids. Twenty-three phytoconstituents were identified, represented mainly by chlorogenic acid, followed by ferulic acid, caffeic acid, and sinapic acid. The tested hydroalcoholic extract was able to inhibit the growth of all tested bacteria and yeast on agar Petri dishes at 3 mg/disc with mean growth inhibition zone ranging from 8.00 ± 0.00 mm for Enterococcus cloacae (E. cloacae) to 36.33 ± 0.58 mm for Staphylococcus epidermidis. Minimal inhibitory concentration ranged from 12.5 mg/mL to 200 mg/mL and the hydroalcoholic extract from D. flabellifolia exhibited a bacteriostatic and fungistatic character. In addition, D. flabellifolia hydroalcoholic extract possessed a good ability to scavenge different free radicals as compared to standard molecules. Molecular docking studies on the identified phyto-compounds in bacterial, fungal, and human peroxiredoxin 5 receptors were performed to corroborate the in vitro results, which revealed good binding profiles on the examined protein targets. A standard atomistic 100 ns dynamic simulation investigation was used to further evaluate the interaction stability of the promising phytocompounds, and the results showed conformational stability in the binding cavity. The obtained results highlighted the medicinal use of D. flabellifolia as source of bioactive compounds, as antioxidant, antibacterial, and antifungal agent.

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Optimizing the Sunitinib for cardio-toxicity and thyro-toxicity by scaffold hopping approach

Cited by 35 publications

References 43 publications

Thymus musilii Velen. Methanolic Extract: In Vitro and In Silico Screening of Its Antimicrobial, Antioxidant, Anti-Quorum Sensing, Antibiofilm, and Anticancer Activities

Thymus musilii Velen. Methanolic Extract: In Vitro and In Silico Screening of Its Antimicrobial, Antioxidant, Anti-Quorum Sensing, Antibiofilm, and Anticancer Activities

A Comprehensive Study to Unleash the Putative Inhibitors of Serotype2 of Dengue Virus: Insights from an In Silico Structure-Based Drug Discovery

Phytochemical Analysis, Antioxidant, and Antimicrobial Activities of Ducrosia flabellifolia: A Combined Experimental and Computational Approaches

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