Design, synthesis and docking studies of some novel (R)-2-(4′-chlorophenyl)-3-(4′-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo [1,2-c]pyrimidin-4-ol derivatives as antitubercular agents

Barot, Kuldipsinh P.; Jain, Sourabh; Gupta, Nitesh; Kremer, Laurent; Singh, Shubhra; Takale, Vijay; Joshi, Kruti; Ghate, Manjunath

doi:10.1016/j.ejmech.2014.06.019

Cited by 28 publications

(12 citation statements)

References 43 publications

(47 reference statements)

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“…All the other enzymes were targeted one time (~2.2% each) and are shown in Table 1. Four manuscripts did not aim for enzymes: two analyzed an iron-dependent regulator (IdeR) gene [21,22] (with PDB coding for 1U8R for both of them), one analyzed a Filamenting temperature-sensitive mutant (FtsZ) protein [23] (with PDB coding for 1RLU), and one made a pharmacophore-based QSAR, comparing isoniazid with derivatives [24].…”

Section: Resultsmentioning

confidence: 99%

Predictive Power of In Silico Approach to Evaluate Chemicals against M. tuberculosis: A Systematic Review

et al. 2019

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Mycobacterium tuberculosis (Mtb) is an endemic bacterium worldwide that causes tuberculosis (TB) and involves long-term treatment that is not always effective. In this context, several studies are trying to develop and evaluate new substances active against Mtb. In silico techniques are often used to predict the effects on some known target. We used a systematic approach to find and evaluate manuscripts that applied an in silico technique to find antimycobacterial molecules and tried to prove its predictive potential by testing them in vitro or in vivo. After searching three different databases and applying exclusion criteria, we were able to retrieve 46 documents. We found that they all follow a similar screening procedure, but few studies exploited equal targets, exploring the interaction of multiple ligands to 29 distinct enzymes. The following in vitro/vivo analysis showed that, although the virtual assays were able to decrease the number of molecules tested, saving time and money, virtual screening procedures still need to develop the correlation to more favorable in vitro outcomes. We find that the in silico approach has a good predictive power for in vitro results, but call for more studies to evaluate its clinical predictive possibilities.

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Section: Resultsmentioning

confidence: 99%

Predictive Power of In Silico Approach to Evaluate Chemicals against M. tuberculosis: A Systematic Review

et al. 2019

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“…To obtain insights into potential toxicities of the highly active 3-((1 Z ,14 E )-1-chloro-3-(phenylimino)prop-1-enyl)-2H-chromen-2-one hybrids, compounds ( 1b, 1c, 1e, 1h, 1h and 1k ) were examined for their cytotoxicity against Vero cells, at concentrations 10 times their actual MIC value. A compound is considered toxic if it causes more than 50% inhibition of normal cells at a concentration 10-fold higher than its MIC [ 48 ]. The results are stated in table 3 .…”

Section: Resultsmentioning

confidence: 99%

Functionalization of 3-chloroformylcoumarin to coumarin Schiff bases using reusable catalyst: an approach to molecular docking and biological studies

et al. 2018

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Recently, heterogeneous catalysts have been explored eximiously in the synthesis of heterocyclic compounds. Therefore, here we used solid-supported heterogeneous silica sulfuric acid as a catalyst for the synthesis of Schiff's base of 3-chloroformylcoumarin in view of simplified procedure, reusability and acceptable efficiency, which are required in organic synthesis. An efficient and facile methodology is preferred for synthesis of a class of chromeno-3-substituted derivatives (1a–1l) with good yields. The molecular docking results showed excellent binding interactions with the Mycobacterium tuberculosis InhA-D148G mutant (PDB: 4DQU). The same biomolecules were screened for their in vitro anti-tubercular activity against the M.tb H37Rv strain and antimicrobial studies. Physico-chemistry, toxicity prediction with IC50 value and bioactivity score were also calculated for title compounds. Most active compounds were further tested for cytotoxicity studies and exhibited low-level cytotoxicity against Vero cells. The suggested conjugates are promising lead compounds for the subsequent investigation in search of new anti-tubercular agents. All the conjugates were obtained within the range and followed the Lipinski rule of 5, indicating more ‘drug-like’ nature.

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“…Plates were read after completion of Weeks 1 and 2 using inverted enlarging mirror plate reader and graded for growth and no growth. The MIC was defined as the lowest drug concentration that prevented growth of bacteria (Barot et al, ; Kaniga et al, ; Soares de Melo et al, ).…”

Section: Methodsmentioning

confidence: 99%

Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N‐(4‐[pyridin‐2‐yloxy]benzyl)arylamine derivatives as potential antitubercular agents

Verma

Boshoff

Arora

et al. 2019

Drug Development Research

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A new series of novel triclosan (2,4,4 0 -trichloro-2 0 -hydroxydiphenylether) analogues were designed, synthesized, and screened for their in vitro antimycobacterial and antibacterial activities. Most of the compounds showed significant activity against Mycobacterium tuberculosis H37Rv strain with minimum inhibitory concentration (MIC) values in 20-40 μM range in GAST/Fe medium when compared with triclosan (43 μM) in the first week of assay, and after additional incubation, seven compounds, that is, 2a, 2c, 2g, 2h, 2i, 2j, and 2m, exhibited MIC values at the concentration of 20-40 μM. The compounds also showed more significant activity against Bacillus subtilis and Staphylococcus aureus. The synthesized compounds showed druggable properties, and the predicted ADME (absorption, distribution, metabolism, and excretion)properties were within the acceptable limits. The in silico studies predicted better interactions of compounds with target protein residues and a higher dock score in comparison with triclosan. Molecular dynamics simulation study of the most active compound 2i was performed in order to further explore the stability of the proteinligand complex and the protein-ligand interaction in detail. K E Y W O R D Smolecular dynamics, mycobacterial enoyl-reductase (InhA), pyridine, triclosan

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Design, synthesis and docking studies of some novel (R)-2-(4′-chlorophenyl)-3-(4′-nitrophenyl)-1,2,3,5-tetrahydrobenzo[4,5] imidazo [1,2-c]pyrimidin-4-ol derivatives as antitubercular agents

Cited by 28 publications

References 43 publications

Predictive Power of In Silico Approach to Evaluate Chemicals against M. tuberculosis: A Systematic Review

Predictive Power of In Silico Approach to Evaluate Chemicals against M. tuberculosis: A Systematic Review

Functionalization of 3-chloroformylcoumarin to coumarin Schiff bases using reusable catalyst: an approach to molecular docking and biological studies

Synthesis, evaluation, molecular docking, and molecular dynamics studies of novel N‐(4‐[pyridin‐2‐yloxy]benzyl)arylamine derivatives as potential antitubercular agents

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