Pyrazolyl Thioureas and Carbothioamides with an NNSN Motif against MSSA and MRSA

Delpe-Acharige, Anjana; Zhang, Man; Eschliman, Kayla; Dalecki, Alex G.; Covarrubias‐Zambrano, Obdulia; Minjarez-Almeida, Azriel; Shrestha, Tejaswi; Lewis, Tanji; Alibrahim, Fatimah; Leonard, Sophia; Roberts, Riana; Tebeje, Anteneh; Malalasekera, Aruni P.; Wang, Hongwang; Kalubowilage, Madumali; Wolschendorf, Frank; Kutsch, Olaf; Bossmann, Stefan H.

doi:10.1021/acsomega.0c04513

Cited by 7 publications

(5 citation statements)

References 28 publications

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“…reported a series of 3APs bearing a thiourea moiety in N1 (compounds 1, Figure 4) with sub-micromolar activity against Methicillin-sensitive Staphylococcus aureus (MSSA) and Methicillin-resistant S. aureus (MRSA) in the presence of bioavailable copper. This study clearly established the suitability of using pyrazolyl thioureas for the treatment of these types of infections [29].…”

Section: Anti-infective 3apssupporting

confidence: 57%

Amino-Pyrazoles in Medicinal Chemistry: A Review

Lusardi

Spallarossa

Brullo

2023

IJMS

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A pyrazole nucleus is an easy-to-prepare scaffold with large therapeutic potential. Consequently, the search for new pyrazole-based compounds is of great interest to the academic community as well as industry. In the last ten years, a large number of papers and reviews on the design, synthesis, and biological evaluation of different classes of pyrazoles and many pyrazole-containing compounds have been published. However, an overview of pyrazole derivatives bearing a free amino group at the 3, 4, or 5 position (namely, 3-aminopyrazoles, 4-aminopyrazoles, and 5-aminopyrazoles, respectively) and their biological properties is still missing, despite the fact that aminopyrazoles are advantageous frameworks able to provide useful ligands for receptors or enzymes, such as p38MAPK, and different kinases, COX and others, as well as targets important for bacterial and virus infections. With the aim to fill this gap, the present review focuses on aminopyrazole-based compounds studied as active agents in different therapeutic areas, with particular attention on the design and structure-activity relationships defined by each class of compounds. In particular, the most relevant results have been obtained for anticancer/anti-inflammatory compounds, as the recent approval of Pirtobrutinib demonstrates. The data reported here are collected from different databases (Scifinder, Web of Science, Scopus, Google Scholar, and Pubmed) using “aminopyrazole” as the keyword.

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Section: Anti-infective 3apssupporting

confidence: 57%

Amino-Pyrazoles in Medicinal Chemistry: A Review

Lusardi

Spallarossa

Brullo

2023

IJMS

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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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“…1 were approved for therapeutic use. 17,18 Various thiourea derivatives are being explored as potential antibacterial agents, such as 3-trifluoromethyl group on phenyl thiourea derivative A demonstrated potent anti-MRSA activity with minimum inhibitory concentration (MIC) ranging 0.25–2 μg mL −1 , 19 thiourea derivatives incorporated in hippuric acid moiety B inhibited S. aureus with MIC 3.12 μg mL −1 , 20 and pyrazolyl thiourea derivative C with NNSN motif (extended thiourea motifs enables binding of copper) showed MRSA inhibition with MIC 0.15 μM, 21 Quinoline amino piperidine hybrid D exhibited potent inhibitory activity against M. tuberculosis with MIC 1.72 μg mL −1 , 22 some thiourea derivatives E showed potent inhibition against M. tuberculosis with MIC 0.78 μg mL −1 (ref. 23) and thiourea derivatives containing 1,3,4-thiadiazoles F , 24 arylthiazole derivative appended with d -glucose G , 25 and benzothiazole derivative appended with d -glucose H 26 exhibited potent antibacterial activity against S. aureus with MIC 0.78 μg mL −1 (Fig.…”

Section: Introductionmentioning

confidence: 99%