Uridine derivatives: Antifungal, PASS outcomes, ADME/T, drug-likeliness, molecular docking and binding energy calculations

Shamsuddin, Tahmida; Hosen, Anowar; Alam, Muhammad Shaiful; Emran, Talha Bin; Kawsar, Sarkar M. A.

doi:10.5455/medscience.2021.05.175

Cited by 31 publications

(14 citation statements)

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“…The volume of distribution (VD) of a drug throughout blood and tissue should be used to estimate whether the drug distributes uniformly or not uniformly. Lower VD indicates that the drug concentration in plasma is more significant, and the medication cannot diffuse to the tissues as effectively [70]. In this case, most molecules had low VD levels, while some had intermediate VD values.…”

Section: Resultsmentioning

confidence: 99%

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Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Akash

Aovi

Azad

et al. 2023

Preprint

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Triple-negative breast cancer accounts for 10-15% of all breast tumors (TNBC). Triple-negative breast cancer lacks either estrogen or progesterone receptors (ER or PR), producing either too little or too much HER2. (All three tests result in "negative" results for the cells.) These cancers are more common in women under 40 who are Black or have the BRCA1 mutation. TNBC differs from other types of invasive breast cancer in that it has fewer treatment options, a worse prognosis, and grows and spreads more quickly (outcome). So, first of all, the protein of triple-negative breast cancer was collected from the PDB database having the most stable configuration, and a natural bioactive molecule, Scutellarein, was selected. Scutellarein is well-known to possess anti-cancer properties, so its derivatives were chosen to design anti-cancer drugs through computational tools. In this case, the functional group has applied and modified structural activity relationship methods. Then, the pass prediction score was taken, which indicates the probability of active (Pa) and the probability of inactive (Pi). After that, other in-silco approaches, such as the ADMET parameter, and quantum calculation by Density Functional Theory (DFT), have been conducted. Finally, molecular docking and dynamics have been evaluated against TNBC to determine the binding affinity and stability. Scutellarein derivatives (DM03 at -10.7 kcal/mol, DM04 at -11.0 kcal/mol) have been reported to have a maximum tendency for binding against TNBC. Besides, the molecular dynamic simulation was performed at 100ns and described by root-mean-square deviation (RMSD) and root-mean-square fluctuation (RMSF), which are much more stable compounds. The pharmacokinetics specifications for a suitable therapeutic candidate were satisfied by these molecules, like as non-carcinogenic, minimal to aquatic and non-aquatic toxicity. Almost all the molecules are highly soluble in the aqueous system. These all-computational data suggested that they might be suitable as a medication for the inhibition of TNBC, and further experimental studies should be carried out.

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Section: Resultsmentioning

confidence: 99%

“…Lower VD indicates that the drug concentration in plasma is more significant, and the medication cannot diffuse to the tissues as effectively [70]. In this case, most molecules had low VD levels, while some had intermediate VD values.…”

Section: Admet Data Predictionmentioning

confidence: 99%

Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Akash

Aovi

Azad

et al. 2023

Preprint

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“…To estimate the relative binding free energy of the interaction, the protein–ligand complexes obtained from the ligand docking were submitted for rescoring using Molecular mechanics combined with Generalized Born Surface Area (MM-GBSA) calculations . The Surface Generalized Born (SGB) model and the variable dielectric (VD) and Optimized Potentials for Liquid Simulations of the Extending Force Field Coverage for Drug-Like Small Molecules (OPLS3e) force field , were selected for the analysis while other parameters were kept constant. A more negative value of MM-GBSA free energies implies a more substantial BE .…”

Section: Methodsmentioning

confidence: 99%

Computational Target-Based Screening of Anti-MRSA Natural Products Reveals Potential Multitarget Mechanisms of Action through Peptidoglycan Synthesis Proteins

et al. 2022

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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the leading causes of bacterial infections in both healthcare and community settings. MRSA can acquire resistance to any current antibiotic, which has major implications for its current and future treatment options. As such, it is globally a major focus for infection control efforts. The mechanical rigidity provided by peptidoglycans in the bacteria cell walls makes it a promising target for broad-spectrum antibacterial drug discovery. The development of drugs that can target different stages of the synthesis of peptidoglycan in MRSA may compromise the integrity of its cell wall and consequently result in the rapid decline of diseases associated with this drug-resistant bacteria. The present study is aimed at screening natural products with known in vitro activities against MRSA to identify their potential to inhibit the proteins involved in the biosynthesis of the peptidoglycan cell wall. A total of 262 compounds were obtained when a literature survey was conducted on anti-MRSA natural products (AMNPs). Virtual screening of the AMNPs was performed against various proteins (targets) that are involved in the biosynthesis of the peptidoglycan (PPC) cell wall using Schrödinger software (release 2020–3) to determine their binding affinities. Nine AMNPs were identified as potential multitarget inhibitors against peptidoglycan biosynthesis proteins. Among these compounds, DB211 showed the strongest binding affinity and interactions with six protein targets, representing three stages of peptidoglycan biosynthesis, and thus was selected as the most promising compound. The MD simulation results for DB211 and its proteins indicated that the protein-ligand complexes were relatively stable over the simulation period of 100 ns. In conclusion, DB211 showed the potential to inhibit six proteins involved in the biosynthesis of the peptidoglycan cell wall in MRSA, thus reducing the chance of MRSA developing resistance to this compound. Therefore, DB211 provided a starting point for the design of new compounds that can inhibit multiple targets in the biosynthesis of the peptidoglycan layer in MRSA.

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“…39 The Gaussian 09 soware package was employed to conduct geometry optimization and subsequent renement of all the synthesized analogs. 40 For optimization, the density functional theory (DFT) approach with the 3-21G basis set, incorporating Becke's and Lee, Yang, and Parr's (LYP) (B) functional, was utilized. 41,42 During this optimization process, water was chosen as the solvent environment.…”

Section: Computational Studiesmentioning

confidence: 99%

A synergistic investigation of azo-thiazole derivatives incorporating thiazole moieties: a comprehensive exploration of their synthesis, characterization, computational insights, solvatochromism, and multimodal biological activity assessment

Muhammed Aziz,

Hassan,

Amin

et al. 2023

RSC Adv.

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Uridine derivatives: Antifungal, PASS outcomes, ADME/T, drug-likeliness, molecular docking and binding energy calculations

Cited by 31 publications

References 0 publications

Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Computational investigation of Scutellarein derivatives as an inhibitor against triple-negative breast cancer by Quantum calculation, and drug-designed approaches

Computational Target-Based Screening of Anti-MRSA Natural Products Reveals Potential Multitarget Mechanisms of Action through Peptidoglycan Synthesis Proteins

A synergistic investigation of azo-thiazole derivatives incorporating thiazole moieties: a comprehensive exploration of their synthesis, characterization, computational insights, solvatochromism, and multimodal biological activity assessment

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