1,2,3-Triazole derivatives as antitubercular agents: synthesis, biological evaluation and molecular docking study

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.

show abstract

“…If the selectivity index (SI) is ≥ 10, the compounds are processed further for drug development [17].…”

Section: Selectivity Indexmentioning

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

View full text Add to dashboard Cite

show abstract

“…Many scientific reports reveals that 1,2,3‐triazole derivatives showed many biological activities including antimicrobial,, anticancer, anticonvulsant, anti‐inflammatory, analgesic and antiviral . Some of the triazoles have been used as cytotoxic and anti‐tubular agents . Apart from this diverse biological activity, triazoles have been used in chemical biology, material science and polymer chemistry .…”

Section: Introductionmentioning

confidence: 99%

Regioselective Synthesis, Antibacterial, Molecular Docking and Fingerprint Applications of 1‐Benzhydrylpiperazine Derivatized 1,4‐Disubstituted 1,2,3‐Triazoles

et al. 2018

View full text Add to dashboard Cite

A series of ten 1,4‐Disubstituted 1,2,3‐Triazoles having 1‐benzhydrylpiperazine chemical scaffold were synthesized by one pot Cu (I) catalyzed click reaction and evaluated for their antibacterial activity against Escherichia Coli and Staphylococcus aureus by agar well diffusion method. Amongst all, 2‐chloro‐6‐fluorobenzyl substituted 1,2,3‐Triazole 7 e and 2,4‐dichlorobenzyl Triazole 7 f found to be more active compared to the Ciprofloxacin. To rationalize the binding interaction of compounds and the protein at active site, we performed Molecular docking study using a bacterial DNA Gyrase B protein. The docking energy of 2‐chloro‐6‐fluorobenzyl substituted Triazole 7 e and 2,4‐dichlorobenzyl Triazole 7 f was observed as −22.498 and −22.569 kcalmol−1 in comparison to reference drug Ciprofloxacin whose docking energy is −22.072 kcal mol−1. It also makes several hydrogen bonds with our conserved residue Ser55, Asp81 and Ile86. Furthermore, several hydrophobic contacts were also observed within the pocket. Finally, Latent fingerprint detection study indicated that the compound unsubstituted Triazole 7 a powder shows good adhesion and finger ridge details without back ground staining. The demonstrated method can be applied to detect fingerprints on all types of smooth surfaces and hence, it can be easily adopted for latent fingerprint detection. The in vitro and in silico activities conclusively revealed that our lead compounds may be used as a novel antibacterial agents.

show abstract

“…[64] 14. Biological Importance of Triazoles Triazolesa nd their derivatives are an interesting and important class of heterocyclic compoundst hat have been widely investigated and identified to hold great potential for various biological applications,including as antimicrobial, [65,66] analgesic, [67] anticonvulsant, [68] anti-inflammatory, [69] anticancer, [70][71] antihypertensive, [72] antimalarial, [73] anti-HIV, [74] hypoglycemic, [75] antidepressant, [76] antitubercular, [77,78] antioxidant, [79] antiviral, [80] anthelmintic, [81] anti-TNF (tumor necrosis factor), [82] antihistaminic, [83] antithyroid, [84] antiproliferative, [85] and antiasthmatic agents, [86] as well as in insecticides [87] and plant-growth regulators. [88] Owing to their structural similarities, triazoles have been used to mimic peptidea nd disulfide bonds, to link functional groupst ogethera nd for bioconjugationw ith various functional groups to increaset heir metabolic stabilitya nd peptidefunctions.…”

Section: -Chloro-1-(6-aryl-2-chloroquinoline-3-yl)-[124]-striazolementioning

confidence: 99%

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

Kamal

Kumar

2016

Chemistry An Asian Journal

View full text Add to dashboard Cite

The organic chemistry of hypervalent organoiodine compounds has been an area of unprecedented development. This surge in interest in the use of hypervalent iodine compounds has mainly been owing to their highly selective oxidizing properties, environmentally benign character and commercial availability. Hypervalent iodine reagents have also been used as an alternative to toxic heavy metals, owing to their low toxicity and ease of handling. Hypervalent organoiodine(III) reagents are versatile oxidants that have been successfully employed to extend the scope of selective oxidative transformations of complex organic molecules in synthetic chemistry. This Focus Review concerns the tandem in situ generation and 1,5-electrocyclization of N-heteroaryl nitrilimines into fused triazoles. We describe the importance of recently developed hypervalent-organoiodine(III)-catalyzed oxidative cyclization reactions, building towards the conclusion that hypervalent iodine chemistry is a promising frontier for oxidative cyclization, in particular of hydrazones, for the synthesis of fused triazoles.

show abstract

1,2,3-Triazole derivatives as antitubercular agents: synthesis, biological evaluation and molecular docking study

Abstract: A library of thirty one 1,2,3-triazole derivatives efficiently prepared via click chemistry and evaluated for their antitubercular, antioxidant, and cytotoxic activities.

Cited by 163 publications

References 49 publications

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

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

Regioselective Synthesis, Antibacterial, Molecular Docking and Fingerprint Applications of 1‐Benzhydrylpiperazine Derivatized 1,4‐Disubstituted 1,2,3‐Triazoles

Hypervalent‐Iodine(III)‐Mediated Oxidative Methodology for the Synthesis of Fused Triazoles

Contact Info

Product

Resources

About