Convergent synthesis, <scp>free radical</scp> scavenging, <scp>Lineweaver‐Burk</scp> plot exploration, hemolysis and in silico study of novel <scp>indole‐phenyltriazole</scp> hybrid bearing acetamides as potent urease inhibitors

Khan, Wajiha; Abbasi, Muhammad Athar; Rehman, Azizur; Siddiqui, Sabahat Zahra; Nazir, Majid; Shah, Syed Adnan Alı; Raza, Hussain; Hassan, Mubashir; Shahid, Muhammad; Seo, Sung Yum

doi:10.1002/jhet.4006

Cited by 11 publications

(3 citation statements)

References 53 publications

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“…HCl was added to adjust pH 5-6. The precipitates were ltered, washed and dried to get desired cyclized product, 5 [35].…”

Section: Synthesis Of 5-[3-(1h-indol-3-ylmentioning

confidence: 99%

Convergent Synthesis, Kinetics and Computational Comprehensions of Indole- (Phenyl)triazole Bi-heterocycles Amalgamated with Propanamides as Elastase Inhibitors

Shakila,

Abbasi,

Rehman

et al. 2024

Preprint

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In the study presented here, 4-(1H-indol-3-yl)butanoic acid was sequentially converted into ethyl 4-(1H-indol-3-yl)butanoate, 4-(1H-indol-3-yl)butanohydrazide and 5-[3-(1H-indol-3-yl)propyl]-1,2,4-triazole-2-thiol as a nucleophile. In a parallel series of reactions, various electrophiles were synthesized by reacting aryl amines with 3-bromopropanoyl chloride to afford N-(aryl)-3-bromopropanamides. Then the nucleophilic substitution reaction of 5 was carried out with different electrophiles, to achieve final bi-heterocyclic derivative. The structural confirmation of all the synthesized compounds was done by IR, 1H-NMR, 13C-NMR and CHN analysis data. The inhibitory effects of these bi-heterocyclic propanamides were evaluated against elastase, and all these molecules were identified as potent inhibitors relative to the standard used. The kinetics mechanism was ascribed by evaluating the Lineweaver–Burk plots, which revealed that compound 9d inhibited elastase competitively to form an enzyme–inhibitor complex. The inhibition constant Ki calculated from Dixon plots for this compound was 0.51 µM. These molecules also exhibited mild cytotoxicity toward red blood cell membranes, when analyzed through hemolysis. So, these molecules might be deliberated as nontoxic medicinal scaffolds for dealing with the elastase related ailments such as lungs diseases, cyclic neutropenia, pruritic skin disease and liver infection.

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“…HCl was added to adjust pH 5-6. The precipitates were ltered, washed and dried to get desired cyclized product, 5 [35].…”

Section: Synthesis Of 5-[3-(1h-indol-3-ylmentioning

confidence: 99%

Convergent Synthesis, Kinetics and Computational Comprehensions of Indole- (Phenyl)triazole Bi-heterocycles Amalgamated with Propanamides as Elastase Inhibitors

Shakila,

Abbasi,

Rehman

et al. 2024

Preprint

Self Cite

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“…Khan et al [78] reported the synthesis of indole-phenyltriazole hybrids with acetamides as antiurease agents. (IC 50 = 0.49 µM) with C 2 H 5 in 2-position and CH 3 in 6-position on the phenyl ring also showed efficient activity due to the presence of two EDGs.…”

Section: Triazolesmentioning

confidence: 99%

“…Khan et al [ 78 ] reported the synthesis of indole‐phenyltriazole hybrids with acetamides as antiurease agents. Compound 147a (IC 50 = 1.44 µM) with unsubstituted phenyl ring described significant activity towerd thiourea (IC 50 = 4.72 µM).…”

Section: Triazolesmentioning

confidence: 99%

An overview of the privileged synthetic heterocycles as urease enzyme inhibitors: Structure–activity relationship

Sepehri,

Khedmati

2023

Archiv der Pharmazie

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Urease is a metalloenzyme including two Ni2+ ions, found in some plants, bacteria, fungi, microorganisms, invertebrate animals, and animal tissues. Urease acts as a significant virulence factor, mainly in catheter blockage and infective urolithiasis as well as in the pathogenesis of gastric infection. Therefore, studies on urease lead to novel synthetic inhibitors. In this review, the synthesis and antiurease activities of a collection of privileged synthetic heterocycles such as (thio)barbiturate, (thio)urea, dihydropyrimidine, and triazol derivatives were described and discussed according to structure–activity relationship findings in search of the best moieties and substituents that are answerable for encouraging the desired activity even more potent than the standard. It was found that linking substituted phenyl and benzyl rings to the heterocycles led to potent urease inhibitors.

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Convergent Synthesis, Kinetics, and Computational Studies of Indole(Phenyl)Triazole Bi‐Heterocycles Modified With Propanamides as Elastase Inhibitors

Shakila,

Abbasi,

Aziz‐ur‐Rehman

et al. 2024

Chemistry & Biodiversity

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Biological screening combined with the synthesis of heterocyclic compounds with numerous functions is the most effective approach available for pharmacological assessment. In the under taken research that is presented here, 4‐(1H‐indol‐3‐yl)butanoic acid was sequentially converted into 4‐(1H‐indol‐3‐yl)butanoate, 4‐(1H‐indol‐3‐yl)butanohydrazide and 5‐[3‐(1H‐indol‐3‐yl)propyl]‐1,2,4‐triazole‐2‐thiol as a nucleophile. The structural confirmation of all the synthesized compounds was done by IR, 1H‐NMR, 13C‐NMR and CHN analysis data. The enzyme inhibitory effects of these bi‐heterocyclic propanamides were evaluated against elastase, and Oleanolic acid with IC50 value 13.453 ± 0.015 µM was used as a standard. The kinetics mechanism was ascribed by Lineweaver–Burk plots, which revealed that compound 9d inhibited elastase competitively. The inhibition constant Ki calculated from Dixon plots for this compound was 0.51 μM. Compound 9d's activity (IC50 = 0.142 ± 0.014 µM) significantly increased when a slightly bulky ethyl group was replaced for the solitary methyl group in 9c at the para position. However, compound 9e's activity was significantly lower (IC50 = 38.338 ± 0.993µM). These molecules also exhibited mild cytotoxicity. So, these molecules might be deliberated as nontoxic medicinal scaffolds for dealing with the elastase related ailments such as lungs diseases, cyclic neutropenia, pruritic skin disease and liver infection.

show abstract

Convergent synthesis, free radical scavenging, Lineweaver‐Burk plot exploration, hemolysis and in silico study of novel indole‐phenyltriazole hybrid bearing acetamides as potent urease inhibitors

Cited by 11 publications

References 53 publications

Convergent Synthesis, Kinetics and Computational Comprehensions of Indole- (Phenyl)triazole Bi-heterocycles Amalgamated with Propanamides as Elastase Inhibitors

Convergent Synthesis, Kinetics and Computational Comprehensions of Indole- (Phenyl)triazole Bi-heterocycles Amalgamated with Propanamides as Elastase Inhibitors

An overview of the privileged synthetic heterocycles as urease enzyme inhibitors: Structure–activity relationship

Convergent Synthesis, Kinetics, and Computational Studies of Indole(Phenyl)Triazole Bi‐Heterocycles Modified With Propanamides as Elastase Inhibitors

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