Density Functional Theory Calculations of Enzyme–Inhibitor Interactions in Medicinal Chemistry and Drug Design

Rozhenko, Alexander

doi:10.1007/978-94-017-9257-8_7

Cited by 8 publications

(8 citation statements)

References 111 publications

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“…the density functional theory (DFT) computational process (Rozhenko 2014). ADMET filtration has been applied to check the toxicity of the compounds (Hou and Wang 2008).…”

Section: Dhfrmentioning

confidence: 99%

“…Electronic structure (molecular orbital) and the effect of substituent of drug-like molecules have significant role in the drug efficiency (Rozhenko 2014). A molecular function can be used to calculate chemical and physical properties.…”

Section: Quantum Chemistry Calculationmentioning

confidence: 99%

“…It indicates (Fig. 8) the electronic excitation energy necessary to compute the molecular reactivity and stability of the compounds (Rozhenko 2014;Zhan et al 2003). Details of DFT analysis are given in Table 4.…”

Section: Density Functional Theory Analysismentioning

confidence: 99%

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Sulfonamide derivatives as Mycobacterium tuberculosis inhibitors: in silico approach

Pradhan¹,

Sinha²

2018

In Silico Pharmacol.

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Both DHPS (dihydropteroate synthase) and DHFR (dihydrofolate reductase) play important physiological roles in the survivability of Mycobacterium tuberculosis (MTB). Sulfonamides are the potent drugs to monitor growth and proliferation of MTBs by inhibiting the activity of DHPS and DHFR which could explain the mechanism of action of these molecules. In this work, 102 heterocyclic sulfonamides (HSF) have been screened by discovery studio molecular docking programme to search the best suitable molecule for the treatment of MTBs. Lipinski's rule of five protocols is followed to screen drug likeness of these molecules and ADMET (absorption, distribution, metabolism, excretion and toxicity) filtration has been used to value their toxicity. Only fourteen molecules are found to obey the Lipinski's rule and able to cross the ADMET filter. A small difference between HOMO and LUMO energy signifies the electronic excitation energy which is essential to calculate molecular reactivity and stability of the best docked compound and easy activation of drug in the protein environment. Both 4-amino-N-(6-hydroxypyridin-2-yl)benzenesulfonamide (M1) and 4-amino-N-(9H-carbazol-2-yl)benzenesulfonamide (M2) show the best theoretical efficiency with DHPS and DHFR, respectively. These compounds are also found to bind to the adenine-thymine region of tuberculosis DNA.

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“…the density functional theory (DFT) computational process (Rozhenko 2014). ADMET filtration has been applied to check the toxicity of the compounds (Hou and Wang 2008).…”

Section: Dhfrmentioning

confidence: 99%

Section: Quantum Chemistry Calculationmentioning

confidence: 99%

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Sulfonamide derivatives as Mycobacterium tuberculosis inhibitors: in silico approach

Pradhan¹,

Sinha²

2018

In Silico Pharmacol.

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“…This is comparable to the reaction free energy, which is frequently used to describe chemical reactions in QM theory. Therefore, the most straightforward strategy to find new effective medication ingredients and to change the existing pharmaceuticals would likely be to maximize the enzyme–substrate negative interaction energy under control of classical QM methods, ab initio or density functional theory (DFT) . In Utkov, a full viewpoint on employing the DFT for calculations of ligand-protein complexes is provided.…”

Section: Introductionmentioning

confidence: 99%

In Silico Screening of Active Compounds in Garri for the Inhibition of Key Enzymes Linked to Diabetes Mellitus

Enyoh

Maduka

Wang

et al. 2022

ACS Food Sci. Technol.

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Through in silico screening, this study seeks to demonstrate a connection between ethnopharmacological claims and the bioactive components found in Garri against potential targets for diabetes. The process of molecular docking involving different bonding modes of compounds in Garri with active cavities of target receptors for proteins human pancreatic alpha-amylase (HPA) and human lysosomal acid-alpha-glucosidase (GAA) was carried out in autodock vina. Density functional theory was used for quantum chemical analysis, while ADME/T properties of the top binding compounds were predicted using the Admetsar and Swissadme database. From the results, (20E)-6-hydroxycholesta-9(11),20( 22)-diene-3,23-dione, 25-dedhydrotigogenin, cochlioquinone B, and psi-diosgenin, showed the best docking results (> −8.1 to −9.8 kcal/mol), when compared with the standard control drugs acarbose (−7.9 kcal/mol) and 1-deoxynojirimycin (< −5.1 kcal/mol). The results from the ADME/T prediction also revealed that the compounds had good pharmacokinetic properties. The study provided insights into the development of better inhibitors to treat diabetes from garri.

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“…Drug likeness has been examined following Lipinski's rule of five filter (Lipinski et al 2001). The molecular orbitals are used to calculate the electronic configuration, molecular reactivity and stability of the compounds by density functional theory (DFT) computational process (Rozhenko 2014). Pharmacophore map generation has also done to observe steric and electronic features of best docked amides that ensured the optimal interactions with a receptor (Pantothenate Synthetase) and to block its biological response (Wermuth et al 1998).…”

Section: Introductionmentioning

confidence: 99%

High throughput screening against pantothenate synthetase identifies amide inhibitors against Mycobacterium tuberculosis and Staphylococcus aureus

Pradhan¹,

Sinha²

2018

In Silico Pharmacol.

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Pantothenate is a crucial enzyme for the synthesis of coenzyme A and acyl carrier protein in Mycobacterium tuberculosis and Staphylococcus aureus. It is indispensable for the growth and survival of these bacteria. Amides analogs are designed and have been used as inhibitors of pantothenate synthetase. Molecular docking approach has been used to design and predict the drug activity of molecule to the specific disease. In this work, more than hundred amides have been screened by Discovery Studio molecular docking programme to search best suitable molecule for the treatment of Mycobacterium tuberculosis. Pharmacophore generation has been done to recognize the binding modes of inhibitors in the receptor active site. To observe the stability and flexibility of inhibitors molecular dynamics (MD) simulation has been done; Lipinski's rule of five protocols is followed to screen drug likeness and ADMET (absorption, distribution, metabolism, excretion and toxicity) filtration is also used to value toxicity. DFT computation of optimized geometry and derivation of MOs has been used to correlate the drug likeness. The small difference in energy between HOMO and LUMO may help to activate the drug in the protein environment quickly. 2-Hydroxy-5-[(E)-2-{4-[(prop-2-enamido)sulfonyl]phenyl}diazen-1-yl]benzoic acid (M1) shows best theoretical efficiency against Mycobacterium tuberculosis (MTB) pantothenate synthetase and so does 2-hydroxy-5-[(E)-2-{4-[(2-phenylacetamido)sulfonyl]phenyl}diazen-1-yl]benzoic acid (M2) against Staphylococcus aureus pantothenate synthetase. These compounds also bind to Adenine-Thymine region of tuberculosis DNA.

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Density Functional Theory Calculations of Enzyme–Inhibitor Interactions in Medicinal Chemistry and Drug Design

Cited by 8 publications

References 111 publications

Sulfonamide derivatives as Mycobacterium tuberculosis inhibitors: in silico approach

Sulfonamide derivatives as Mycobacterium tuberculosis inhibitors: in silico approach

In Silico Screening of Active Compounds in Garri for the Inhibition of Key Enzymes Linked to Diabetes Mellitus

High throughput screening against pantothenate synthetase identifies amide inhibitors against Mycobacterium tuberculosis and Staphylococcus aureus

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