Pyrazole: an Emerging Privileged Scaffold in Drug Discovery

Alam, Mohammad Abrar

doi:10.4155/fmc-2023-0207

Cited by 17 publications

(7 citation statements)

References 108 publications

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“…In our quest to find antibacterial and antineoplastic agents, ,− we tested these novel benzothiophene compounds against several strains of Gram-positive and Gram-negative bacterial strains. To our delight, we found several compounds with potent activity against Gram-positive bacteria and A.…”

Section: Resultsmentioning

confidence: 99%

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents

Roy,

Budhathoki,

Iqbal

et al. 2024

J. Org. Chem.

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An efficient synthesis of 3-amino-2-formyl-functionalized benzothiophenes by a domino reaction protocol and their use to synthesize a library of novel scaffolds have been reported. Reactions of ketones and 1,3-diones with these amino aldehyde derivatives formed a series of benzothieno[3,2-b]pyridine and 3,4-dihydro-2H-benzothiopheno [3,2-b]quinolin-1-one, respectively. A plausible mechanism for the formation of fused pyridine derivatives by the Friedlander reaction has been elucidated by density functional theory (DFT) calculations. Furthermore, hydrazones were obtained by reacting the aldehyde functional group of benzothiophenes with different hydrazine derivatives. Preliminary screening of these compounds against several bacterial strains and cancer cell lines led to the discovery of several hit molecules. Hydrazone and benzothieno [3,2-b]pyridine derivatives are potent cytotoxic and antibacterial agents, respectively. One of the potent compounds effected ∼97% growth inhibition of the LOX IMVI cell line at 10 μM concentration.

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Section: Resultsmentioning

confidence: 99%

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents

Roy,

Budhathoki,

Iqbal

et al. 2024

J. Org. Chem.

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“…Almost all Schiff bases possess promising ADMT properties (well absorbed, possess good skin permeability, and well metabolized in the liver), which may be due to the presence of the pyrazole moiety in their structures. The pyrazole motif has promising biological applications [18][19][20][21] and is effective in various disease treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Here, we re-synthesized three sets of pyrazole-based Schiff bases (5a-f, 6a-f, and 7a-f) via the reaction of 1a-f with 2, 3, and 4, respectively, according to the literature procedures mentioned in our previous works [35,36] (Scheme 1). The pyrazole scaffold has received considerable attention because of its promising biological applications [18][19][20][21]. For examples, Mortada et al (2024) synthesized a pyrazoletriazole derivative, E, that displayed powerful inhibition of α-glucosidase and α-amylase enzymes.…”

Section: Chemistrymentioning

confidence: 99%

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

Naglah,

Almehizia,

Al-Wasidi

et al. 2024

Pharmaceuticals

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In this innovative research, we aim to reveal pyrazole-based Schiff bases as new multi-target agents. In this context, we re-synthesized three sets of pyrazole-based Schiff bases, 5a–f, 6a–f, and 7a–f, to evaluate their biological applications. The data from in vitro biological assays (including antioxidant and scavenging activities, anti-diabetes, anti-Alzheimer’s, and anti-inflammatory properties) of the pyrazole-based Schiff bases 5a–f, 6a–f, and 7a–f showed that the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f possess the highest biological properties among the compounds evaluated. The cytotoxicity against lung (A549) and colon (Caco-2) human cancer types, as well as normal lung (WI-38) cell lines, was evaluated. The data from the cytotoxicity investigation demonstrated that the three Schiff bases 5d, 5e, and 7a are active against lung (A549) cells, while the two Schiff bases 5e and 7a exhibited the highest cytotoxicity towards colon (Caco-2) cells. Additionally, the enzymatic activities against caspase-3 and Bcl-2 of the six pyrazole-based Schiff bases 5a, 5d, 5e, 5f, 7a, and 7f were evaluated. Furthermore, we assessed the in silico absorption, distribution, metabolism, and toxicity (ADMT) properties of the more potent pyrazole-based Schiff bases. After modifying the structures of the six pyrazole-based Schiff bases, we plan to further extend the studies in the future.

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“…The pyrazole scaffold represents a privileged substructure in medicinal chemistry research and a number of pyrazole derivatives have been evaluated as effective compounds in different therapeutic areas [ 10 , 11 , 12 , 13 , 14 , 15 , 16 ], including infectious diseases [ 17 , 18 ] and also against MRSA [ 19 ]. In previous studies, pyrazole derivatives I ( Figure 1 ) showed significative antibacterial activity against Gram-positive antibiotic-resistant strains [ 20 ].…”

Section: Introductionmentioning

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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Pyrazole: an Emerging Privileged Scaffold in Drug Discovery

Cited by 17 publications

References 108 publications

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents

Domino Reaction Protocol to Synthesize Benzothiophene-Derived Chemical Entities as Potential Therapeutic Agents

Exploring the Potential Biological Activities of Pyrazole-Based Schiff Bases as Anti-Diabetic, Anti-Alzheimer’s, Anti-Inflammatory, and Cytotoxic Agents: In Vitro Studies with Computational Predictions

New Pyrazolyl Thioureas Active against the Staphylococcus Genus

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