Predictive Qualitative Structure-Property/Activity Relationships for Drug Design in Some of Antimycobacterial Pyrrole Derivatives

Belaidi, Salah; Belaidi, Houmam; Kerassa, Aicha; Saoula, Mohamed; Bouzidi, Djemoui

doi:10.1166/qm.2016.1386

Cited by 4 publications

(4 citation statements)

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“…Also, the alkylic group substituted pyrrole derivatives have been investigated using computational tools to predict the SAR features in smart agent design for antimycobacterial activity. [35] Previously we reported the synthesis of strychnos alkaloids using a DDQ cyclization reaction. [36] In this study, we introduce a novel mechanism involving DDQ-catalyzed oxidative coupling between ketoximes and DEAD "diethyl acetylene dicarboxylate", paving the way for the synthesis of diversely substituted pyrroles (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

“…have reported a detailed investigation of the MMNPC molecules in the framework of pyrrole; they have used the DFT methods to examine the vibrational analysis, UV‐Vis spectrum, NBO analysis, and NMR spectrum, alongside MEP analysis and local reactivity descriptor analysis; the results imply they promise as a potent inhibitor for treating ovarian cancer and potential for novel drug development. Also, the alkylic group substituted pyrrole derivatives have been investigated using computational tools to predict the SAR features in smart agent design for antimycobacterial activity [35] …”

Section: Introductionmentioning

confidence: 99%

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Advancing Pyrrole Synthesis through DDQ Catalysis: A Comprehensive Research Incorporating DFT, ADMT, and Molecular Docking Analysis

Serdaroğlu,

Uludağ,

Üstün

2024

ChemistrySelect

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The construction of pyrroles is an important heterocyclic group comprising many compounds with interesting properties that have led to numerous applications in various fields. We delineate a new synthetic method for the rapid construction of tree‐substituted pyrroles from readily available ketoximes as starting materials and also a new mechanism and method has been proposed. It is presented that substituted pyrroles were efficiently synthesized in high yields (up to 81 % yield) through the cyclization reaction of starting ketoximes mediated by 2,3‐dichlor‐5,6‐dicyanobenzoquinone (DDQ). Utilizing this protocol various pyrrole derivatives were synthesized from diethyl acetylene dicarboxylate (DEAD). We then developed the dehydrogenation reaction mechanism of this formation, also studied in detail, also all synthesized compounds were analyzed in detail by spectroscopic techniques (FT‐IR, 1H NMR, 13CNMR) which were compared with the computational data estimated at B3LYP/6‐311G** level. The thermochemical and electronic properties of the pyrroles were evaluated after optimizing and then confirming the equilibrium structures. ADMT scores were also considered to estimate/elucidate the possible bioavailability tendencies as well as the toxicity. In addition, the interactions of the optimized molecules were evaluated by molecular docking methods against BSA “Bovine Serum Albumin” and LIF “Leukemia Inhibitory Factor”. The results obtained from this study will ideally provide a fundamental source in contemporary drug design in terms of both the key electronic properties underlying the possible reactivity features and toxicity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Advancing Pyrrole Synthesis through DDQ Catalysis: A Comprehensive Research Incorporating DFT, ADMT, and Molecular Docking Analysis

Serdaroğlu,

Uludağ,

Üstün

2024

ChemistrySelect

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“…Therefore, it is crucial to test whether the proposed derivatives ( 2H , 6H , 7H , and 9H ) satisfy the ADME prerequisites as anticancer drugs. The final step in drug design and drug discovery is to perform quantitative structure–activity relationships (QSAR) using the multilinear regression statistical approach that predicts the antitumor activity as a function of the quantum chemical parameters from quantum chemical computation and the physicochemical parameters from virtual screening and drug-like computation [ 7 , 24 , 32 , 33 , 34 , 35 , 36 , 37 ]. In medicinal chemistry, there is a principle indicating that structurally similar molecules may have similar biological activities [ 38 ].…”

Section: Introductionmentioning

confidence: 99%

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

Khaled

Elshakre

Noamaan

et al. 2022

IJMS

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Computational chemistry, molecular docking, and drug design approaches, combined with the biochemical evaluation of the antitumor activity of selected derivatives of the thiouracil-based dihydroindeno pyrido pyrimidines against topoisomerase I and II. The IC50 of other cell lines including the normal human lung cell line W138, lung cancer cell line, A549, breast cancer cell line, MCF-7, cervical cancer, HeLa, and liver cancer cell line HepG2 was evaluated using biochemical methods. The global reactivity descriptors and physicochemical parameters were computed, showing good agreement with the Lipinski and Veber’s rules of the drug criteria. The molecular docking study of the ligands with the topoisomerase protein provides the binding sites, binding energies, and deactivation constant for the inhibition pocket. Various biochemical methods were used to evaluate the IC50 of the cell lines. The QSAR model was developed for colorectal cell line HCT as a case study. Four QSAR statistical models were predicted between the IC50 of the colorectal cell line HCT to correlate the anticancer activity and the computed physicochemical and quantum chemical global reactivity descriptors. The predictive power of the models indicates a good correlation between the observed and the predicted activity.

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“…Quantitative Structure Activity Relationships (QSARs) [8,25,[31][32][33][34][35][36] attempt to establish a correlation between the physicochemical parameters of chemical structures and their biological activity. There is a general principle of medicinal chemistry on which QSAR is based which connects the biological activity of a compound to its molecular structure, which states that structurally similar molecules may have similar biological activities [37].…”

Section: Introductionmentioning

confidence: 99%

Density Functional Theory, Chemical Reactivity, Pharmacological Potential and Molecular Docking of Dihydrothiouracil-Indenopyridopyrimidines with Human-DNA Topoisomerase II

Elshakre

Noamaan

Moustafa

et al. 2020

IJMS

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In this work, three computational methods (Hatree-Fock (HF), Møller–Plesset 2 (MP2), and Density Functional Theory (DFT)) using a variety of basis sets are used to determine the atomic and molecular properties of dihydrothiouracil-based indenopyridopyrimidine (TUDHIPP) derivatives. Reactivity descriptors of this system, including chemical potential (µ), chemical hardness (η), electrophilicity (ω), condensed Fukui function and dual descriptors are calculated at B3LYP/6-311++ G (d,p) to identify reactivity changes of these molecules in both gas and aqueous phases. We determined the molecular electrostatic surface potential (MESP) to determine the most active site in these molecules. Molecular docking study of TUDHIPP with topoisomerase II α and β is performed, predicting binding sites and binding energies with amino acids of both proteins. Docking studies of TUDHIPP versus etoposide suggest their potential as antitumor candidates. We have applied Lipinski, Veber’s rules and analysis of the Golden triangle and structure activity/property relationship for a series of TUDHIPP derivatives indicate that the proposed compounds exhibit good oral bioavailability. The comparison of the drug likeness descriptors of TUDHIPP with those of etoposide, which is known to be an antitumor drug, indicates that TUDHIPP can be considered as an antitumor drug. The overall study indicates that TUDHIPP has comparable and even better descriptors than etoposide proposing that it can be as effective antitumor drug, especially 2H, 6H and 7H compounds.

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Predictive Qualitative Structure-Property/Activity Relationships for Drug Design in Some of Antimycobacterial Pyrrole Derivatives

Cited by 4 publications

References 0 publications

Advancing Pyrrole Synthesis through DDQ Catalysis: A Comprehensive Research Incorporating DFT, ADMT, and Molecular Docking Analysis

Advancing Pyrrole Synthesis through DDQ Catalysis: A Comprehensive Research Incorporating DFT, ADMT, and Molecular Docking Analysis

A Computational QSAR, Molecular Docking and In Vitro Cytotoxicity Study of Novel Thiouracil-Based Drugs with Anticancer Activity against Human-DNA Topoisomerase II

Density Functional Theory, Chemical Reactivity, Pharmacological Potential and Molecular Docking of Dihydrothiouracil-Indenopyridopyrimidines with Human-DNA Topoisomerase II

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