Design, Synthesis, and Characterization of Some Hybridized Pyrazolone Pharmacophore Analogs against <i>Mycobacterium tuberculosis</i>

Krishnasamy, Sivakumar Kullampalayam; Namasivayam, Vigneshwaran; Mathew, Sincy; Eakambaram, Ragavendran S.; Ibrahim, Ibrahim A.; Natarajan, Adhirajan; Senthilkumar, Palaniappan

doi:10.1002/ardp.201600019

Cited by 14 publications

(14 citation statements)

References 23 publications

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“…Sivakumar et al [109] prepared two series of hybridized pyrazolone analogues and determined their antitubercular effect. The most potent compounds 151 and 152 (Fig.…”

Section: Anti-tuberculosis Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

149

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a b s t r a c tThe pyrazolone structural motif is a critical element of drugs aimed at different biological end-points. Medicinal chemistry researches have synthesized drug-like pyrazolone candidates with several medicinal features including antimicrobial, antitumor, CNS (central nervous system) effect, anti-inflammatory activities and so on. Meanwhile, SAR (Structure-Activity Relationship) investigations have drawn attentions among medicinal chemists, along with a plenty of analogues have been derived for multiple targets. In this review, we comprehensively summarize the biological activity and SAR for pyrazolone analogues, wishing to give an overall retrospect and prospect on the pyrazolone derivatives.

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“…Sivakumar et al [109] prepared two series of hybridized pyrazolone analogues and determined their antitubercular effect. The most potent compounds 151 and 152 (Fig.…”

Section: Anti-tuberculosis Agentsmentioning

confidence: 99%

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Zhao

Dai

et al. 2020

European Journal of Medicinal Chemistry

149

View full text Add to dashboard Cite

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“…The antitubercular activity of the synthesized compounds and standard drugs were assessed against Mycobacterium tuberculosis using Microplate alamar blue assay (MABA) [15]. This methodology is non-toxic, uses a thermally stable reagent and shows good correlation with proportional and BACTEC radiometric method.…”

Section: Antitubercular Activitymentioning

confidence: 99%

Development of New Pyrazole Hybrids as Antitubercular Agents: Synthesis, Biological Evaluation and Molecular Docking Study

Shaikh¹,

Zaheer²,

Mokale³

et al. 2017

Int J Pharm Pharm Sci

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Objective: Synthesis of new 1, 3-diphenyl pyrazole derivatives 9(a-f) and 10(a-f) using molecular hybridization approach and evaluation of their antitubercular and cytotoxic studies. Methods:The structures of synthesized compounds were confirmed by 1 H NMR, 13 C NMR and mass spectra. The antitubercular activity of compounds and standard drugs were assessed against Mycobacterium tuberculosis using Microplate alamar blue assay (MABA). The cytotoxic activities were performed by Sulforhodamine B (SRB) assay. The molecular docking and in silico ADME prediction studies were also performed by using Schrodinger. Results:The results reveal that compounds 9c, 9d, 10c and 10d exhibited substantial antitubercular potential with MIC<20 μM. The cytotoxic studies revealed that active compounds (9c, 9d, 10c and 10d) are non-toxic to HeLa cancer cell lines with the selectivity index>10. The molecular docking study was performed to study the binding orientation and affinity of synthesized compounds for InhA enzyme. Conclusion:The study explored that 1, 3-diphenyl pyrazole hybrid coupled with well-known antitubercular drugs could be a potential lead for antitubercular agents. In silico molecular docking, study helps to identify their corresponding intermolecular ligand-protein interactions with target enzyme. Also, ADME prediction studies revealed that the compounds were in acceptable range to have good pharmacokinetic parameters.

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“…In the sequence, 1U8R codes for an IdeR (iron-dependent regulator) protein complexed with DNA and was evaluated two times (4%) [21,22]. 2IYQ (Shikimate kinase complexed with ADP), 1WE2 (shikimate kinase in complex with MGADP and shikimic acid) and 2IYZ (Shikimate kinase in complex with shikimate-3-phosphate and ADP) were all studied twice by the same group (4% each) [13,54]. Finally, 1ECL (7K N-terminal fragment of E. coli DNA topoisomerase I), 1MW8 (complex between E. coli DNA Topoisomerase I and Single-Stranded DNA) and 1MW9 (another E. coli DNA Topoisomerase I and Single-Stranded DNA) were also studied two times each (4%) [49,50].…”

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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Design, Synthesis, and Characterization of Some Hybridized Pyrazolone Pharmacophore Analogs against Mycobacterium tuberculosis

Cited by 14 publications

References 23 publications

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Pyrazolone structural motif in medicinal chemistry: Retrospect and prospect

Development of New Pyrazole Hybrids as Antitubercular Agents: Synthesis, Biological Evaluation and Molecular Docking Study

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

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