Synthesis, Structural Characterization, DFT Calculations, and Molecular Docking of a Novel Quinoline Derivative

Jamal, Asif; Faizi, Md. Serajul Haque; DEGE, Necmi

doi:10.1016/j.molstruc.2023.137251

Cited by 14 publications

(1 citation statement)

References 96 publications

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“…Conversely, the LUMO, signifying the ability to accept electrons, usually resides near peptide bonds with electron-withdrawing groups. By introducing electron-donating groups in the HOMO orbital or electron-withdrawing groups in the LUMO orbital, it is possible to augment the energy gap, which may enhance the stability of antimicrobial peptides [ 71 , 72 , 73 , 74 ].…”

Section: Discussionmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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Soybean phytophthora blight is a severe menace to global agriculture, causing annual losses surpassing USD 1 billion. Present crop loss mitigation strategies primarily rely on chemical pesticides and disease-resistant breeding, frequently surpassed by the pathogens’ quick adaptive evolution. In this urgent scenario, our research delves into innovative antimicrobial peptides characterized by low drug resistance and environmental friendliness. Inhibiting chitin synthase gene activity in Phytophthora sojae impairs vital functions such as growth and sporulation, presenting an effective method to reduce its pathogenic impact. In our study, we screened 16 previously tested peptides to evaluate their antimicrobial effects against Phytophthora using structure-guided drug design, which involves molecular docking, saturation mutagenesis, molecular dynamics, and toxicity prediction. The in silico analysis identified AMP_04 with potential inhibitory activity against Phytophthora sojae’s chitin synthase. Through three rounds of saturation mutagenesis, we pin-pointed the most effective triple mutant, TP (D10K, G11I, S14L). Molecular dynamic simulations revealed TP’s stability in the chitin synthase-TP complex and its transmembrane mechanism, employing an all-atom force field. Our findings demonstrate the efficacy of TP in occupying the substrate-binding pocket and translocation catalytic channel. Effective inhibition of the chitin synthase enzyme can be achieved. Specifically, the triple mutant demonstrates enhanced antimicrobial potency and decreased toxicity relative to the wild-type AMP_04, utilizing a mechanism akin to the barrel-stave model during membrane translocation. Collectively, our study provides a new strategy that could be used as a potent antimicrobial agent in combatting soybean blight, contributing to sustainable agricultural practices.

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Section: Discussionmentioning

confidence: 99%

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Ran,

Shehzadi,

Liang

et al. 2024

IJMS

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Novel Cyclopropyl Appended 1,3‐Thiazole‐2‐Imines as Multi‐Target Agents: Design, Synthesis, Biological Evaluation and Computational Studies

Zaman,

Saeed,

ul Muntaha

et al. 2024

Asian J Org Chem

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In the present work, we developed a library of novel cyclopropyl clubbed 1,3‐thiazole‐2‐imines (6a‐h) from the efficient cyclization between multistep synthesized thiourea precursors and ethyl 2‐chloroacetoacetate. Subsequently, the in vitro biological screening including antibacterial, α‐amylase, and proteinase K inhibition was carried out to assess their inhibition potential. In general, all synthesized compounds revealed moderate to significant potency. The compound (6a) with no substitution at the phenyl ring exhibited the highest inhibitory activity amongst all, with an IC50 value of 1.716 ± 0.062 µM against proteinase K. Fortunately, this compound (6a) also unfolded the most significant antibacterial potential against B. subtilis showing 20 mm zone of inhibition. The compound (6d) possessing a naphthyl ring was found to be the most potent inhibitor of amylase displaying IC50 value of 1.634 ± 0.002 µM. Diverse substitution patterns on 2‐imino‐1,3‐thiazoline pharmacophores provided a valuable basis for SAR analysis. Computational studies including DFT, molecular electrostatic potential, molecular docking, and ADMET were conducted to predict the chemical reactivity, ligand‐protein binding interactions, and drug‐likeness of synthesized compounds. Hence these studies highlighted our synthesized compounds as novel antibacterial, α‐amylase, and proteinase K inhibitors.

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Benzylidenehydrazine Derivatives: Synthesis, Antidiabetic Evaluation, Antioxidation, Mode of Inhibition, DFT and Molecular Docking Studies

Seboletswe,

Kumar,

Gcabashe

et al. 2024

Chemistry & Biodiversity

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Diabetes mellitus (DM) is a metabolic condition that is a profound health concern across the globe due to its contribution to the increased mortality rate. It affects millions of people around the world and is associated with severe complications among people diagnosed with it. Herein, we report the synthesis of benzylidenehydrazine derivatives as well as their evaluation as α‐glucosidase and α‐amylase inhibitors including their antioxidant testing. Generally, all the synthesized derivatives were more potent inhibitors of α‐amylase than of α‐glucosidase. Specifically, 2,4 fluoro substituted analogue 9 (IC50 =116.19 µM) emerged as the strongest α‐amylase inhibitor with ~5‐fold superior activity in comparison to the standard drug, acarbose (IC50 = 600 µM). Compounds 18 (IC50 = 240.59) and 19 (IC50 = 198.32 µM) displayed the strongest NO scavenging activity compared to Trolox (IC50 = 272.36 µM). In addition, the enzyme kinetic studies indicated that compound 9 acts as a non‐competitive inhibitor of α‐amylase. Finally, density functional theory and molecular docking studies for compound 9 were conducted to explore its structural and electronic properties as well as to determine protein‐ligand interactions, respectively to decipher its observed activity.

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Synthesis, Structural Characterization, DFT Calculations, and Molecular Docking of a Novel Quinoline Derivative

Cited by 14 publications

References 96 publications

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Rationally Designed Novel Antimicrobial Peptides Targeting Chitin Synthase for Combating Soybean Phytophthora Blight

Novel Cyclopropyl Appended 1,3‐Thiazole‐2‐Imines as Multi‐Target Agents: Design, Synthesis, Biological Evaluation and Computational Studies

Benzylidenehydrazine Derivatives: Synthesis, Antidiabetic Evaluation, Antioxidation, Mode of Inhibition, DFT and Molecular Docking Studies

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