Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study

Bhatt, Jaimin D.; Chudasama, Chaitanya J.; Patel, K. C.

doi:10.1016/j.bmc.2015.11.018

Cited by 67 publications

(49 citation statements)

References 20 publications

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“…In continuation of our previous work and considering the pharmacological importance of 1,3‐diarylpyrazole, DHPMs, and pyridines, we have attempted the synthesis of desired hybrid molecules equipped with three pharmacophoric nucleus in single molecular framework. With an aim to eliminate the use of toxic organic solvents, expensive catalysts, and harsh reaction conditions, we have modified, optimized, and developed Biginelli reaction condition utilizing TEAA as catalyst and reaction medium as well yielding the hybrid entities in green, clean, and inexpensive manner.…”

Section: Introductionsupporting

confidence: 57%

Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non‐Classical Antifolates and Their Efficacy Against Plasmodium falciparum

Bhatt

Chudasama

Patel

2017

Archiv der Pharmazie

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A series of diarylpyrazole clubbed dihydropyrimidine derivatives (J1-J30) was synthesized under microwave-assisted heating conditions by employing Biginelli reaction methodology and utilizing triethylammonium acetate both as a catalyst and as reaction medium, leading towards a greener reaction pathway. The synthesized entities were screened for their antimalarial efficacy against a Plasmodium falciparum strain in vitro. The active entities (J9, J15, J21, J25, and J27) obtained out of the in vitro screening were further evaluated for their enzyme inhibitory potency against the Pf-DHFR enzyme in vitro as well as in silico using Glide. Furthermore, the active scaffolds were tested for their cytotoxicity against Vero cells, proving their nontoxic behavior and selectivity. The ADME parameters were also evaluated and predicted in silico, indicating good oral bioavailability of the compounds.

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Section: Introductionsupporting

confidence: 57%

Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non‐Classical Antifolates and Their Efficacy Against Plasmodium falciparum

Bhatt

Chudasama

Patel

2017

Archiv der Pharmazie

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“…Synthetic analogues of pyrazole are known to exhibit significant antitubercular activity especially 1, 3-diphenyl pyrazole motif is known to be a potent antitubercular agent ( fig. 1) [9]. Even though isoniazid (INH) has been the most widely used treatment for tuberculosis and its latent infections, it suffers from two pitfalls as enzymatic acetylation of isoniazid by Nacetyltransferase (NATs) and it's associated liver toxicity.…”

Section: Introductionmentioning

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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“…Bhatt et al. reported that pyrazole‐triazolo[1,5‐ a ]pyrimidine hybrid derivative 176 possess anti‐TB activity at MIC of 0.39 μg/mL, which was higher than rifampin (MIC = 0.5 μg/mL) . Detailed molecular docking study indicates compounds of this class to inhibit enoyl ACP reductase (InhA) enzyme of M. tuberculosis .…”

Section: Pyrazolesmentioning

confidence: 99%

New structural classes of antituberculosis agents

Kumar

Patel

Jain

2017

Medicinal Research Reviews

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Tuberculosis (TB), one of the deadliest diseases is shattering the health and socioeconomic status of the society. The emergence of multidrug resistant (MDR) and extremely drug resistant (XDR) strains has provided unprecedented lethal character to TB. The development of MDR and XDR strains of TB results in more deaths, longer duration of therapy, and appearance of the disease in the immunocompromised patients. Because of the development of rapid resistance by Mycobacterium tuberculosis, researchers are confronted with serious challenges in combating TB. For instance, the need for potency and specificity in therapeutic agents approaching clinics, and the increasing demand of low toxicity due to long duration of treatment. Recently, it is proposed that such challenges could be addressed by a shift from contemporary or known classes of drugs to new scaffold-containing or entirely new structural classes of drugs that possibly act on the previously unknown targets, resulting in possibly less instances of resistance development. The exploitation of advances made in the biology of TB in the last and present decades have created opportunities to discover a large number of new structural classes that specifically targets TB by molecular mechanism of action(s) unknown earlier. We have earlier reviewed new structural classes of anti-TB agents up to year 2005. This review covers literature reports of the subsequent 10 years on the discovery of new structural classes of synthetic anti-TB agents. Due to the availability of large number of research reports, we have divided new compounds in 38 structural classes, 368 structures, and 307 references.

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Pyrazole clubbed triazolo[1,5-a]pyrimidine hybrids as an anti-tubercular agents: Synthesis, in vitro screening and molecular docking study

Cited by 67 publications

References 20 publications

Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non‐Classical Antifolates and Their Efficacy Against Plasmodium falciparum

Diarylpyrazole Ligated Dihydropyrimidine Hybrids as Potent Non‐Classical Antifolates and Their Efficacy Against Plasmodium falciparum

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

New structural classes of antituberculosis agents

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