Recent Synthetic Methodologies Towards the Synthesis of Pyrazoles

Aziz, Hira; Zahoor, Ameer Fawad; Shahzadi, Irum; Irfan, Ali

doi:10.1080/10406638.2019.1614638

Cited by 9 publications

(6 citation statements)

References 72 publications

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“…Heterocycles, especially nitrogen-containing compounds, have attracted considerable attention due to their wide spectrum and important biological uses in the fields of medicines, pharmacology, pharmaceutics, and pharmaceuticals. Heterocycles furans and benzofuran [16], pyrazoles [17], thiophenes [18], oxadiazoles [19], 1,2,4-Amino-triazines [20], thiadiazoles [21], imidazoles benzimidazoles, triazoles, pyridines, pyrimidines, benzoxazoles, benzothiazoles [22,23], etc., constitute the integral part of most of the clinical drugs and ther-apeutics to treat various diseases such as antiviral, anti-cancer, anti-bacterial, anti-allergic, anti-diabetic, analgesic, anti-histamine, anti-inflammatory, anti-tuberculosis, hemolytic, anti-convulsant, thrombolytic, anti-neurodegenerative, anti-leprosy, anti-tumor, antifungal, antipyretics, antihypertensive, dehydrogenase kinase inhibitor, herbicidal, etc. [16][17][18][19][20][21][22][23].…”

Section: Heterocycles As Hcv-ns5b Inhibitorsmentioning

confidence: 99%

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches

Irfan,

Faisal,

Ahmad

et al. 2023

Biomedicines

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Benzofuran, 1,3,4-oxadiazole, and 1,2,4-triazole are privileged heterocyclic moieties that display the most promising and wide spectrum of biological activities against a wide variety of diseases. In the current study, benzofuran-1,3,4-oxadiazole BF1–BF7 and benzofuran-1,2,4-triazole compounds BF8–BF15 were tested against HCV NS5B RNA-dependent RNA polymerase (RdRp) utilizing structure-based screening via a computer-aided drug design (CADD) approach. A molecular docking approach was applied to evaluate the binding potential of benzofuran-appended 1,3,4-oxadiazole and 1,2,4-triazole BF1–BF15 molecules. Benzofuran-1,3,4-oxadiazole scaffolds BF1–BF7 showed lesser binding affinities (−12.63 to −14.04 Kcal/mol) than benzofuran-1,2,4-triazole scaffolds BF8–BF15 (−14.11 to −16.09 Kcal/mol) against the HCV NS5B enzyme. Molecular docking studies revealed the excellent binding affinity scores exhibited by benzofuran-1,2,4-triazole structural motifs BF-9 (−16.09 Kcal/mol), BF-12 (−15.75 Kcal/mol), and BF-13 (−15.82 Kcal/mol), respectively, which were comparatively better than benzofuran-based HCV NS5B inhibitors’ standard reference drug Nesbuvir (−15.42 Kcal/mol). A molecular dynamics simulation assay was also conducted to obtain valuable insights about the enzyme–compounds interaction profile and structural stability, which indicated the strong intermolecular energies of the BF-9+NS5B complex and the BF-12+NS5B complex as per the MM-PBSA method, while the BF-12+NS5B complex was the most stable system as per the MM-GBSA calculation. The drug-likeness and ADMET studies of all the benzofuran-1,2,4-triazole derivatives BF8–BF15 revealed that these compounds possessed good medicinal chemistry profiles in agreement with all the evaluated parameters for being drugs. The molecular docking affinity scores, MM-PBSA/MM-GBSA and MD-simulation stability analysis, drug-likeness profiling, and ADMET study assessment indicated that N-4-fluorophenyl-S-linked benzofuran-1,2,4-triazole BF-12 could be a future promising anti-HCV NS5B RdRp inhibitor therapeutic drug candidate that has a structural agreement with the Nesbuvir standard reference drug.

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Section: Heterocycles As Hcv-ns5b Inhibitorsmentioning

confidence: 99%

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches

Irfan,

Faisal,

Ahmad

et al. 2023

Biomedicines

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“…There is an urgent demand and necessity for the designing, discovery, and development of novel curative candidates active against all forms of Mtb [ 8 , 9 , 10 , 11 , 12 , 13 ]. Heterocycles-based ring systems such as quinoxalines, coumarins, benzothiazoles, benzoxazoles, thiadiazoles, benzofurans, and oxadiazoles, etc., constitute a powerful backbone of different chemotherapeutic agents with a wide spectrum of biological activities in medicine, pharmacology, and pharmaceutics [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. Benzofuran ( Figure 1 ) is a five-membered oxygen containing a fused heterocyclic compound first synthesized by Perkin in 1870 [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13

et al. 2023

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Benzofuran and 1,3,4-oxadiazole are privileged and versatile heterocyclic pharmacophores which display a broad spectrum of biological and pharmacological therapeutic potential against a wide variety of diseases. This article reports in silico CADD (computer-aided drug design) and molecular hybridization approaches for the evaluation of the chemotherapeutic efficacy of 16 S-linked N-phenyl acetamide moiety containing benzofuran-1,3,4-oxadiazole scaffolds BF1–BF16. This virtual screening was carried out to discover and assess the chemotherapeutic efficacy of BF1–BF16 structural motifs as Mycobacterium tuberculosis polyketide synthase 13 (Mtb Pks13) enzyme inhibitors. The CADD study results revealed that the benzofuran clubbed oxadiazole derivatives BF3, BF4, and BF8 showed excellent and remarkably significant binding energies against the Mtb Pks13 enzyme comparable with the standard benzofuran-based TAM-16 inhibitor. The best binding affinity scores were displayed by 1,3,4-oxadiazoles-based benzofuran scaffolds BF3 (−14.23 kcal/mol), BF4 (−14.82 kcal/mol), and BF8 (−14.11 kcal/mol), in comparison to the binding affinity score of the standard reference TAM-16 drug (−14.61 kcal/mol). 2,5-Dimethoxy moiety-based bromobenzofuran-oxadiazole derivative BF4 demonstrated the highest binding affinity score amongst the screened compounds, and was higher than the reference Pks13 inhibitor TAM-16 drug. The bindings of these three leads BF3, BF4, and BF8 were further confirmed by the MM-PBSA investigations in which they also exhibited strong bindings with the Pks13 of Mtb. Moreover, the stability analysis of these benzofuran-1,3,4-oxadiazoles in the active sites of the Pks13 enzyme was achieved through molecular dynamic (MD) simulations at 250 ns virtual simulation time, which indicated that these three in silico predicted bio-potent benzofuran tethered oxadiazole molecules BF3, BF4, and BF8 demonstrated stability with the active site of the Pks13 enzyme.

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“…This has attracted the attention of medicinal researchers to develop novel AChE inhibitors. The heterocyclic scaffolds such as benzofuran [18,19], pyrazole [20], lamivudine [21], quinoxaline-sulfonamide [22], oxadiazole [23][24][25][26], triazole [27,28], phenyl-piperazine-based carbodithioates [29][30][31], and thiadiazole [32,33] have drawn significant attraction in the area of medicinal chemistry due to their remarkable pharmacological and biological activities [34,35]. In particular, benzofuran has attracted researchers because it is so frequent in natural products [36].…”

Section: Introductionmentioning

confidence: 99%

“…Recently, heterocyclic scaffolds containing the benzofuran ring have been reported as potent AChE inhibitors, such as benzofuran-based benzylpyridinium 1a, tacrine-derived benzofuran 1b, coumarin-linked benzofuran 1c, and hydroxypyridinone-containing benzofuran 1d [39][40][41][42] (Figure 2). The heterocyclic scaffolds such as benzofuran [18,19], pyrazole [20], lamivudine [21], quinoxaline-sulfonamide [22], oxadiazole [23][24][25][26], triazole [27,28], phenyl-piperazine-based carbodithioates [29][30][31], and thiadiazole [32,33] have drawn significant attraction in the area of medicinal chemistry due to their remarkable pharmacological and biological activities [34,35]. In particular, benzofuran has attracted researchers because it is so frequent in natural products [36].…”

Section: Introductionmentioning

confidence: 99%

Unfolding the Antibacterial Activity and Acetylcholinesterase Inhibition Potential of Benzofuran-Triazole Hybrids: Synthesis, Antibacterial, Acetylcholinesterase Inhibition, and Molecular Docking Studies

et al. 2023

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In this study, a series of novel benzofuran-based 1,2,4-triazole derivatives (10a–e) were synthesized and evaluated for their inhibitory potential against acetylcholinesterase (AChE) and bacterial strains (E. coli and B. subtilis). Preliminary results revealed that almost all assayed compounds displayed promising efficacy against AChE, while compound 10d was found to be a highly potent inhibitor of AChE. Similarly, these 5-bromobenzofuran-triazoles 10a–e were screened against B. subtilis QB-928 and E. coli AB-274 to evaluate their antibacterial potential in comparison to the standard antibacterial drug penicillin. Compound 10b was found to be the most active among all screened scaffolds, with an MIC value of 1.25 ± 0.60 µg/mL against B. subtilis, having comparable therapeutic efficacy to the standard drug penicillin (1 ± 1.50 µg/mL). Compound 10a displayed excellent antibacterial therapeutic efficacy against the E. coli strain with comparable MIC of 1.80 ± 0.25 µg/mL to that of the commercial drug penicillin (2.4 ± 1.00 µg/mL). Both the benzofuran-triazole molecules 10a and 10b showed a larger zone of inhibition. Moreover, IFD simulation highlighted compound 10d as a novel lead anticholinesterase scaffold conforming to block entrance, limiting the swinging gate, and disrupting the catalytic triad of AChE, and further supported its significant AChE inhibition with an IC50 value of 0.55 ± 1.00 µM. Therefore, compound 10d might be a promising candidate for further development in Alzheimer’s disease treatment, and compounds 10a and 10b may be lead antibacterial agents.

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Recent Synthetic Methodologies Towards the Synthesis of Pyrazoles

Cited by 9 publications

References 72 publications

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches

An Exploration of the Inhibitory Mechanism of Rationally Screened Benzofuran-1,3,4-Oxadiazoles and-1,2,4-Triazoles as Inhibitors of NS5B RdRp Hepatitis C Virus through Pharmacoinformatic Approaches

In Silico Development of Novel Benzofuran-1,3,4-Oxadiazoles as Lead Inhibitors of M. tuberculosis Polyketide Synthase 13

Unfolding the Antibacterial Activity and Acetylcholinesterase Inhibition Potential of Benzofuran-Triazole Hybrids: Synthesis, Antibacterial, Acetylcholinesterase Inhibition, and Molecular Docking Studies

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