Synthesis, antitubercular activity, and molecular modeling studies of analogues of isoliquiritigenin and liquiritigenin, bioactive components from Glycyrrhiza glabra

Gaur, Rashmi; Thakur, Jay Prakash; Yadav, Dharmendra Kumar; Kapkoti, Deepak Singh; Verma, Rajesh; Gupta, Namita; Khan, Feroz; Saikia, Dharmendra; Bhakuni, R. S.

doi:10.1007/s00044-015-1401-1

Cited by 21 publications

(7 citation statements)

References 31 publications

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“…The calculated TPSA values of the designed compounds were within acceptable limits. Further, the distribution of compounds in the human body as indicated by blood-brain barrier coefficient (logBB), apparent Caco-2 permeability, log Kp for skin permeability, the volume of distribution, and plasma protein binding (log Khsa for serum protein binding) were determined to be within the standard range 48 , 49 . All compounds except 3 and 6 possessed good aqueous solubility (Table S1 , Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The rotatable numbers of bonds number was used as a measure of flexibility (cut-off ≤ 10) and bioavailability. Drug distribution depends on several factors, including permeability (indicated by apparent Caco-2 and MDCK permeability, and log Kp for skin permeability), blood-brain barrier (log BBB), volume of distribution, and plasma protein binding (shown as logKhsa for serum protein binding) 48 , 49 , 74 . These ADME descriptors for the designed thieno[3,2-c]pyran analogs were calculated and checked for compliance with standard ranges.…”

Section: Methodsmentioning

confidence: 99%

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Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Yadav

Kumar

Saloni

et al. 2018

Sci Rep

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SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Yadav

Kumar

Saloni

et al. 2018

Sci Rep

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“…The log of octanol/water partition coefficient (LogP), molecular weight (MW), and topological polar surface area (TPSA) values are all factors of both membrane permeability and oral bioavailability. The in silico ADME values determined (Table 4 ) revealed the skin permeability (log Kp) of the design derivatives to be within − 4.83 to − 5.97 cm/s, which is within the acceptable range of − 8.0 to − 1.0 cm/s [ 8 ]. Molar refractivity is the measure of the volume occupied either by an atom or a group of atoms [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

Virtual screening and molecular dynamic simulations of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a Pf-DHODH protein target

Ibrahim

Uzairu

Shallangwa

et al. 2022

Egypt J Med Hum Genet

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Background The processes of drug development and validation are too expensive to be subjected to experimental trial and errors. Hence, the use of the insilico approach becomes imperative. To this effect, the drug-likeness and pharmacokinetic properties of the ten (10) previously designed derivatives of 2-anilino 4-amino substituted quinazolines were carried out. Their predicted ligand binding interactions were also carried out by docking them against the Plasmodium falciparum dihydroorotate dehydrogenase (Pf-DHODH) protein target, and the stability of the complex was determined through dynamic simulations. The drug-likeness and pharmacokinetic characteristics were estimated using the online SwissADME software, while the Molegro Virtual Docker (MVD) software was used for molecular docking. And the dynamic simulation was performed for the duration of 100 ns to verify the stability of the docked complex, with the aid of a Schrödinger program, Desmond. Results The designed derivatives were all found to pass the Lipinski test of drug likeness, while the pharmacokinetic studies result that the skin permeability and molar refractivity values of the derivatives are both within the limits. In addition, except for derivative C-01, most of the derivatives have strong gastrointestinal absorptions and lack Pgp substrate. Furthermore, no derivative inhibited CYP1A2, CYP2C9, or CYP2C19. The docking studies show the better binding affinities between the ligands and Pf-DHODH than those between the atovaquone or chloroquine standards. The derivative C-02, {5-((6,7-dimethoxy-4-((3-nitrobenzyl)amino)quinazolin-2-yl)amino)-2-fluorobenzaldehyde} was found to be the most stable derivative, with a re-rank docking score of − 173.528 kcal/mol and interaction energy of − 225.112 kcal/mol. The dynamic simulation analysis shows that the derivative C-02 forms a stable complex with the protein target over the simulation time. Conclusions The ability of these ligands to form hydrogen bonds, as well as various other interactions, was cited as a factor responsible for their better binding affinity. These findings could aid further the development of enhanced antimalarial drugs.

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“…The Kp includes assessing a compound's biological absorption via the skin and has been used as a source of data for threat assessment on the skin [37]. The developed compounds' log Kp values (Table 5) were all determined to be within the permissible range of − 8.0 to − 1.0 [38].…”

Section: Drug-likeness and Adme Predictionmentioning

confidence: 99%

Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)

et al. 2021

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Background The sixteen (16) designed data set of substituted aryl amine-based triazolopyrimidine were docked against Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) employing Molegro Virtual Docker (MVD) software and their pharmacokinetic property determined through SwissADME predictor. Results The docking studies shows compound D16, 5-((6-methoxy-5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)amino)benzo[b]thiophen-4-ol to be the most interactive and stable derivative (re-rank score = − 114.205 kcal/mol) resulting from the hydrophobic as well as hydrogen interactions. The hydrogen interaction produced one hydrogen bond with the active residues LEU359 (H∙∙H∙∙O) at a bond distances of 2.2874 Å. All the designed derivatives were found to pass the Lipinski rule of five tests, supporting the drug-likeliness of the designed compounds. Conclusion The ADME analysis revealed a perfect concurrence with the Lipinski Ro5, where the derivatives were found to possess good pharmacokinetic properties such as molar refractivity (MR), number of rotatable bonds (nRotb), log of skin permeability (log Kp), blood-brain barrier (BBB). These results could a deciding factor for the optimization of novel antimalarial compounds.

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Synthesis, antitubercular activity, and molecular modeling studies of analogues of isoliquiritigenin and liquiritigenin, bioactive components from Glycyrrhiza glabra

Cited by 21 publications

References 31 publications

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study

Virtual screening and molecular dynamic simulations of the antimalarial derivatives of 2-anilino 4-amino substituted quinazolines docked against a Pf-DHODH protein target

Pharmacokinetic predictions and docking studies of substituted aryl amine-based triazolopyrimidine designed inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH)

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