Theoretical Calculations and Experimental Verification of the Antibacterial Potential of Some Monocyclic β-Lactams Containing Two Synergetic Buried Antibacterial Pharmacophore Sites

Ali, Parvez; Meshram, Jyotsna S.; Youssoufi, Moulay H.; Hadda, Taïbi Ben

doi:10.1080/10426500903095556

Cited by 46 publications

(26 citation statements)

References 14 publications

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“…In contrast to antibacterial agent, the antiviral drug should have (X δ--Y δ-) pharmacophore site with respect of some architectural parameters (dihedral angle = 0-10 degree and distance d x-y = 3-3.5 Å). [33][34][35][36][37][38][39] This can be applied for all compounds described here ( Figure 5). …”

Section: 1 Petra Analysismentioning

confidence: 99%

“…Molecular Polar Surface Area PSA is calculated as a sum of fragment contributions. [33][34][35][36][37][38][39] O-, N-and Scentered polar fragments are considered. PSA has been shown to be a very good descriptor characterizing drug absorption, including intestinal absorption, bioavailability, Caco-2 permeability and blood-brain barrier penetration.…”

Section: Molinspiration Calculationsmentioning

confidence: 99%

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Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents

Genç¹,

Genç²,

Tekin³

et al. 2016

ACSi

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This article demonstrates the synthesis of 1,2,4-triazole derivatives and their applications in medicine particularly as anti-breast cancer agents which is a major issue of the present. The synthesized compounds were characterized by elemental analysis, FT-IR and NMR. DFT was used to study the quantum chemical calculations of geometries and vibrational wave numbers of 3-hydroxynaphthyl and p-tolyl substituted 1,2,4-triazoles in the ground state. The scaled harmonic vibrational frequencies obtained from the DFT method were compared with those of the FT-IR spectra and found good agreement. The synthesized 1,2,4-triazole-naphthyl hybrids were screened for the anticancer activity against MCF-7 breast cancer lines. Among them compounds 3 and 7 showed broad spectrum anticancer activity with IC 50 values 9.7 μM and 7.10 μM, respectively and their activity is comparable to that of the standard drugs. The molecular model for binding between the compounds (1-8) and the active site of BRCA2 was obtained on the basis of the computational docking results and the structure-activity relationship.

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Section: 1 Petra Analysismentioning

confidence: 99%

Section: Molinspiration Calculationsmentioning

confidence: 99%

Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents

Genç¹,

Genç²,

Tekin³

et al. 2016

ACSi

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“…A suitable theoretical concept is that proposed by Ben Hadda et al [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] apropos of definition of pharmacophore site. The best descriptors for studying and identifying the type of pharmacophore site (antibacterial, antiviral or antitumor) are the description in detail of local electrophilicity and the nucleophilicity of each functionalized group and their spatial arrangement.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22] Recently, it has been shown that the kinase inhibition by an organometallic systems under biological condition may be significantly facilitated if a ligand containing an anti-kinase pharmacophore (NH-C=O), a bidentate N,N coordinative site (staurosporine derivatives) and non-toxic metal (ruthenium) are available. [2][3][4][5][6] The cancer inhibition of kinase enzymes through organic drugs has been the subject of different theoretical investigations.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] For these reasons, we constructed a platform of some of the key bioinformatic model in order to predict and characterize the antitumor drugs performance of the tested series of staurosporine-ruthenium(II) complexes. Our aim in this work is to give a deeper insight into the coordination effect of transition metal (ruthenium) to bioactive drug (staurosporine), on the inhibition efficiency of ruthenium-staurosporine complexes ( Figure 1) using POM and DFT analyses.…”

Section: Introductionmentioning

confidence: 99%

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Computational POM and DFT Evaluation of Experimental in-vitro Cancer Inhibition of Staurosporine-Ruthenium(II) Complexes: The Power Force of Organometallics in Drug Design

Hadda¹,

Genç

Masand³

et al. 2015

ACSi

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A computational Petra/Osiris/Molinspiration/DFT(POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of ruthenium-staurosporine complexes 2-4 containing an antitumoral-kinase (TK) pharmacophore sites. The four compounds 1-4 analyzed here were previously screened for their antitumor activity, compounds 2 and 4 are neutral, whereas analogue compound 3 is a monocation with ruthenium(II) centre. The highest anti-antitumor activity was obtained for compounds 3 and 4, which exhibited low IC 50 values (0.45 and 8 nM, respectively), superior to staurosporine derivative (pyridocarbazole ligand 1, 150 · 10 3 nM). The IC 50 of 3 (0.45 nM), represents 20,000 fold increased activity as compared to staurosporine derivative 1. The increase of bioactivity could be attributed to the existence of pi-charge transfer from metal-staurosporine to its (CO δ--NH δ+ ) antitumor pharmacophore site.

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Antimicrobial and Antiquorum‐Sensing Studies. Part 3: Synthesis and Biological Evaluation of New Series of [1,3,4]Thiadiazoles and Fused [1,3,4]Thiadiazoles

El‐Gohary

Shaaban

2015

Archiv der Pharmazie

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New series of [1,3,4]thiadiazoles and fused [1,3,4]thiadiazoles were synthesized. The newly synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus cereus, and Escherichia coli. Compounds 3b and 10a displayed the highest activity against E. coli with MIC value of 78.125 μg/mL. In addition, compound 10a exhibited the highest activity against B. cereus with MIC value of 156.25 μg/mL. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus flavus 3375. Compounds 3b, 5a, 10a, and 12b showed the best activity against A. flavus 3375 with MIC value of 19.531 μg/mL. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds 3b, 5a, and 12b exhibited moderate activity. In vitro cytotoxicity testing of compounds 3b,c, 5a, 6a, 10a, and 12a,b against human normal lung fibroblast (W138) cell line was performed. The in vivo acute toxicity of the same compounds was also tested and the obtained results indicated that compound 10a is the least toxic analog. The same compounds were studied for their DNA-binding affinity and the obtained results showed that compounds 3b, 10a, and 12a,b have moderate DNA-binding affinity.

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Theoretical Calculations and Experimental Verification of the Antibacterial Potential of Some Monocyclic β-Lactams Containing Two Synergetic Buried Antibacterial Pharmacophore Sites

Cited by 46 publications

References 14 publications

Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents

Design, Synthesis, in vitro Antiproliferative Activity, Binding Modeling of 1,2,4,-Triazoles as New Anti-Breast Cancer Agents

Computational POM and DFT Evaluation of Experimental in-vitro Cancer Inhibition of Staurosporine-Ruthenium(II) Complexes: The Power Force of Organometallics in Drug Design

Antimicrobial and Antiquorum‐Sensing Studies. Part 3: Synthesis and Biological Evaluation of New Series of [1,3,4]Thiadiazoles and Fused [1,3,4]Thiadiazoles

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