Synthesis and pharmacological evaluation of 1,3-diaryl substituted pyrazole based (thio)urea derivatives as potent antimicrobial agents against multi-drug resistant <i>Staphylococcus aureus</i> and <i>Mycobacterium tuberculosis</i>

Yaddanapudi, Venkata Madhavi; Ommi, Ojaswitha; Ahmad, Manzoor; Gajula, Siva Nageswara Rao; Wanjari, Parita; Sahu, S. K.; Agnivesh, Puja Kumari; Sahoo, Santosh Kumar; Kalia, Nitin Pal; Sonti, Rajesh; Nanduri, Srinivas; Dasgupta, Arunava; Chopra, Sidharth

doi:10.1039/d3md00079f

Cited by 5 publications

(2 citation statements)

References 68 publications

(93 reference statements)

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“…In conclusion, PTUs here reported could represent a new starting point for the development of new antibacterial pyrazole-based agents [ 35 , 36 , 37 , 38 ] able to counteract strains resistant to common antibiotics and consequently a new therapeutic approach for CF patients [ 39 , 40 , 41 ]. Additional studies will be necessary to identify the mechanism of action of this class of molecules.…”

Section: Discussionmentioning

confidence: 99%

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

Schito,

Caviglia,

Penco

et al. 2024

Pharmaceuticals

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To meet the urgent need for new antibacterial molecules, a small library of pyrazolyl thioureas (PTUs) was designed, synthesized and tested against difficult-to-treat human pathogens. The prepared derivatives are characterized by a carboxyethyl functionality on C4 and different hydroxyalkyl chains on N1. Compounds 1a–o were first evaluated against a large panel of Gram-positive and Gram-negative pathogens. In particular, the majority of PTUs proved to be active against different species of the Staphylococcus genus, with MIC values ranging from 32 to 128 µg/mL on methicillin-resistant Staphylococcus strains, often responsible for severe pulmonary disease in cystic fibrosis patients. Time-killing experiments were also performed for the most active compounds, evidencing a bacteriostatic mechanism of action. For most active derivatives, cytotoxicity was evaluated in Vero cells, and at the tested concentrations and at the experimental exposure time of 24 h, none of the compounds analysed showed significant toxicity. In addition, favourable drug-like, pharmacokinetic and toxicity properties were predicted for all new synthesized derivatives. Overall, the collected data confirmed the PTU scaffold as a promising chemotype for the development of novel antibacterial agents active against Gram-positive multi-resistant strains frequently isolated from cystic fibrosis patients.

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Section: Discussionmentioning

confidence: 99%

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

Schito,

Caviglia,

Penco

et al. 2024

Pharmaceuticals

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“…After that cells were harvested and pUC19 was isolated using QIAprep spin miniprep kit (Qiagen). The topological state of the plasmid was separated in 0.8 % (w/v) agarose with 1X TAE buffer at 70 V for 1 hour by loading 500 ng of untreated pUC19 control and pUC19 extracted from treated cultures [32,33] …”

Section: Methodsmentioning

confidence: 99%

Synthesis and Biological Evaluation of Diphenyl Ether‐Linked Quinolone Derivatives as Antibacterial Agents

Ghouse,

Akhir,

Sinha

et al. 2023

ChemistrySelect

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The increase in the prevalence of multi‐drug‐resistant bacteria poses a significant healthcare challenge. The urgent need to combat the resistant microbes necessitates discovering new antibacterial agents capable of circumventing the existing resistance mechanisms. Targeting DNA gyrase by suitably modifying the fluoroquinolones can lead to antibiotics with better activity and lower incidence of resistance. The substituted diphenyl ethers like triclosan are known to have potent antibacterial activity. In the current study, the hybridisation of diphenyl ether moiety with fluoroquinolones led to the design and synthesis of new compounds with potent inhibitory activity against staphylococcus aureus with MIC 0.5–64 μg/mL and moderately active against mycobacteria with MIC 2–64 μg/mL. The compounds are non‐toxic to Vero cells with a selectivity index >10 to 200. The compounds also inhibited the resistant strains of S. aureus with a MIC ranging from 0.5–64 μg/mL. The synthesised compounds also exhibited potent anti‐biofilm activity against S. aureus. Furthermore, the DNA supercoiling assay revealed the compounds 7 i, 7 o, 7 p and 7 q showed concentration‐dependant DNA‐Gyrase inhibition at 1 μg/mL.

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Exploration of 3‐aryl pyrazole‐tethered sulfamoyl carboxamides as carbonic anhydrase inhibitors

Ommi,

Paoletti,

Bonardi

et al. 2023

Archiv der Pharmazie

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Herein, we report the design and synthesis of two series of pyrazole‐tethered sulfamoyl phenyl acetamides and pyrazole‐tethered sulfamoyl phenyl benzamides. The synthesized compounds were investigated for inhibiting two human carbonic anhydrases, human carbonic anhydrases (hCA) I and II, and those of the bacterial pathogen Mycobacterium tuberculosis, mtCA 1–3. The results indicate that, among the synthesized compounds, pyrazoles with 4‐aminobenzene sulfonamide were more selective toward hCA I and II over mtCAs, and compounds with 3‐aminobenzene sulfonamide were selective toward mtCA 1–3 over hCA I, II. Compound 6g showed significant and selective inhibition toward hCA I and II, with Ki values of 0.0366 and 0.0310 µM, respectively. Compound 5g exhibited the best inhibition toward mtCA 2, with a Ki value of 0.0617 µM. Among the benzamides, compound 9b exhibited significant activity toward mtCA 2, with a Ki value of 0.0696 µM. Selectivity of these compounds was further supported by docking studies. When tested for antitubercular activity, many compounds showed moderate to good inhibition against the Mtb H37Rv strain, with minimum inhibitory concentration (MIC) values in the range of 4–128 µg/mL.

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Synthesis and pharmacological evaluation of 1,3-diaryl substituted pyrazole based (thio)urea derivatives as potent antimicrobial agents against multi-drug resistant Staphylococcus aureus and Mycobacterium tuberculosis

Abstract: The urgent development of newer alternatives has been deemed a panacea for tackling emerging antimicrobial resistance effectively. Herein, we report the design, synthesis, and biological evaluation of 1,3-diaryl substituted pyrazole-based...

Cited by 5 publications

References 68 publications

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

Synthesis and Biological Evaluation of Diphenyl Ether‐Linked Quinolone Derivatives as Antibacterial Agents

Exploration of 3‐aryl pyrazole‐tethered sulfamoyl carboxamides as carbonic anhydrase inhibitors

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