Structure-based design, synthesis and biological evaluation of a newer series of pyrazolo[1,5-a]pyrimidine analogues as potential anti-tubercular agents

Modi, Palmi; Patel, Shivani; Chhabria, Mahesh T.

doi:10.1016/j.bioorg.2019.02.044

Cited by 56 publications

(33 citation statements)

References 27 publications

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“…These pyrimidine hybrids are potential analogs as a cyclin-dependent kinase 2 (CDK2) inhibitors. Pyrimidine fused pyrazole hybrids 47 were synthesized and tested for their anti-tubercular activity against the H37Rv strain [106]. All the tested hybrids showed good to excellent antitubercular activity with MIC values ranging from 0.8 to 50 g/mL (Figure 54).…”

Section: Pyrimidinesmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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The analogs of nitrogen-based heterocycles occupy an exclusive position as a valuable source of therapeutic agents in medicinal chemistry. More than 75% of drugs approved by the FDA and currently available in the market are nitrogen-containing heterocyclic moieties. In the forthcoming decade, a much greater share of new nitrogen-based pharmaceuticals is anticipated. Many new nitrogen-based heterocycles have been designed. The number of novel N-heterocyclic moieties with significant physiological properties and promising applications in medicinal chemistry is ever-growing. In this review, we consolidate the recent advances on novel nitrogen-containing heterocycles and their distinct biological activities, reported over the past one year (2019 to early 2020). This review highlights the trends in the use of nitrogen-based moieties in drug design and the development of different potent and competent candidates against various diseases.

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Section: Pyrimidinesmentioning

confidence: 99%

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

et al. 2020

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“…In recent years, pyrazolo [1,5-a]pyrimidine derivatives have received a special interest due to their diverse biological and pharmacological activities including DNA binding and anti-tubercular, antioxidant, antibacterial and anticancer activities [2][3][4][5][6][7][8]. Among these pyrazolo [1,5-a]pyrimidine derivatives, compound A showed potent antibacterial activity against Escherichia coli and Bacillus subtilis when compared to standard drug (Penicillin) [9].…”

Section: Introductionmentioning

confidence: 99%

Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

et al. 2020

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Pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i were synthesized for evaluation of their in vitro antimicrobial properties against some microorganisms and their immunomodulatory activity. The biological activities of pyrazolo[1,5-a]pyrimidines showed that the pyrazolo[1,5-a]pyrimidines (5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h) displayed promising antimicrobial and immunomodulatory activities. Studying the in silico predicted physicochemical, pharmacokinetic, ADMET and drug-likeness properties for the pyrazolo[1,5-a]pyrimidines 5a–c, 9a–c and 13a–i confirmed that most of the compounds (i) were within the range set by Lipinski’s rule of five, (ii) show higher gastrointestinal absorption and inhibition of some CYP isoforms, and (iii) have a carcinogenicity test that was predicted as negative and hERG test that presented medium risk. Moreover, the molecular docking study demonstrated that the compounds 5c, 9a, 9c, 13a, 13c, 13d, 13e and 13h are potent inhibitors of 14-alpha demethylase, transpeptidase and alkaline phosphatase enzymes. This study could be valuable in the discovery of a new series of drugs.

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“…To study the stability of ligand into the binding site of protein, molecular dynamics (MD) simulations provide the better understanding of ligand through several statistical parameters [ 48 , 49 ]. Several scientific literatures support the reliability and satisfactory stability for the MD run (≤ 10 ns) through in silico endeavor [50] , [51] , [52] , [53] , [54] , [55] . In a similar line of approach, the hit complexes obtained from the evaluation of ADMET and drug-likeliness properties, were subjected for MD simulations using GROMACS 2020.1 to assess the stability of the stability of the ligands ( 2 - 3 ) in the active site of docked complex at various time points up to 10 ns [ 56 , 57 ].…”

Section: Resultsmentioning

confidence: 87%

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

Nagar

Gajjar

Dhameliya

2021

Journal of Molecular Structure

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Severe acute respiratory syndrome has relapsed recently as novel coronavirus causing a life threat to the entire world in the absence of an effective therapy. To hamper the replication of the deadly SARS CoV-2 inside the host cells, systematic in silico virtual screening of total 267,324 ligands from Asinex EliteSynergy and BioDesign libraries has been performed using AutoDock Vina against RdRp. The molecular modeling studies revealed the identification of twenty-one macrocyclic hits ( 2 - 22 ) with better binding energy than remdesivir ( 1 ), marketed SARS CoV-2 inhibitor. Further, the analysis using rules for drug-likeness and their ADMET profile revealed the candidature of these hits due to superior oral bioavailability and druggability. Further, the MD simulation studies of top two hits ( 2 and 3 ) performed using GROMACS 2020.1 for 10 ns revealed their stability into the docked complexes. These results provide an important breakthrough in the design of macrocyclic hits as SARS CoV-2 RNA replicase inhibitor.

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Structure-based design, synthesis and biological evaluation of a newer series of pyrazolo[1,5-a]pyrimidine analogues as potential anti-tubercular agents

Cited by 56 publications

References 27 publications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications

Biological Evaluation and Molecular Docking with In Silico Physicochemical, Pharmacokinetic and Toxicity Prediction of Pyrazolo[1,5-a]pyrimidines

In search of SARS CoV-2 replication inhibitors: Virtual screening, molecular dynamics simulations and ADMET analysis

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