Development of Novel α-Amylase Inhibitors: Synthesis, Molecular Docking, and Biochemical Studies.

IF 2.5 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell Biochemistry and Biophysics Pub Date : 2025-04-29 DOI:10.1007/s12013-025-01759-6

K Ramakrishnan, Reshma Rajan, Lenin Nachimuthu, Premkumar Jayaraj, Chandrakala A Narasimhulu, Pragney Deme, Sanjay Rajagopalan, Akella Sivaramakrishna, S Karthikeyan, Rajagopal Desikan

{"title":"Development of Novel α-Amylase Inhibitors: Synthesis, Molecular Docking, and Biochemical Studies.","authors":"K Ramakrishnan, Reshma Rajan, Lenin Nachimuthu, Premkumar Jayaraj, Chandrakala A Narasimhulu, Pragney Deme, Sanjay Rajagopalan, Akella Sivaramakrishna, S Karthikeyan, Rajagopal Desikan","doi":"10.1007/s12013-025-01759-6","DOIUrl":null,"url":null,"abstract":"The rising prevalence of diabetes as a major non-communicable disease underscores the critical need for effective anti-diabetic agents. The new analogs designed 3a-3j were effectively synthesised and thoroughly characterised using (1H, 13C NMR, FT-IR, GCMS, and HRMS) to investigate their structural biochemical properties. The novel analogs were investigated thoroughly by in silico (molecular docking) and in vitro (anti-oxidant (DPPH, ABTS) activity, anti-inflammation (RBC), modifications of LDL and HDL, thiobarbituric substances, cholesterol efflux assay, and anti-diabetic) assays, validated for α-amylase inhibition. Enzyme inhibition results showed α-amylase IC50 values of 1.79 ± 0.12 μg for compound 3d, 1.75 ± 0.05 μg for compound 3e, and 1.53 ± 0.20 μg for the standard drug acarbose. Among the new molecules, compounds 3c and 3d exhibited the highest inhibitory activity in all performed in silico and in vitro studies. The study demonstrated that inhibitors 3a-3j bind strongly to the active site of human pancreatic α-amylase, highlighting their potential as effective inhibitors. These research findings help to improve the field of developing lead molecules for anti-diabetic agents.","PeriodicalId":510,"journal":{"name":"Cell Biochemistry and Biophysics","volume":" ","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Biochemistry and Biophysics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1007/s12013-025-01759-6","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

The rising prevalence of diabetes as a major non-communicable disease underscores the critical need for effective anti-diabetic agents. The new analogs designed 3a-3j were effectively synthesised and thoroughly characterised using (¹H, ¹³C NMR, FT-IR, GCMS, and HRMS) to investigate their structural biochemical properties. The novel analogs were investigated thoroughly by in silico (molecular docking) and in vitro (anti-oxidant (DPPH, ABTS) activity, anti-inflammation (RBC), modifications of LDL and HDL, thiobarbituric substances, cholesterol efflux assay, and anti-diabetic) assays, validated for α-amylase inhibition. Enzyme inhibition results showed α-amylase IC₅₀ values of 1.79 ± 0.12 μg for compound 3d, 1.75 ± 0.05 μg for compound 3e, and 1.53 ± 0.20 μg for the standard drug acarbose. Among the new molecules, compounds 3c and 3d exhibited the highest inhibitory activity in all performed in silico and in vitro studies. The study demonstrated that inhibitors 3a-3j bind strongly to the active site of human pancreatic α-amylase, highlighting their potential as effective inhibitors. These research findings help to improve the field of developing lead molecules for anti-diabetic agents.

查看原文本刊更多论文

新型α-淀粉酶抑制剂的开发：合成、分子对接和生化研究

糖尿病作为一种主要非传染性疾病的发病率不断上升，这突出表明迫切需要有效的抗糖尿病药物。设计的新类似物3a-3j被有效合成，并通过（1H, 13C NMR, FT-IR， GCMS和HRMS）研究了它们的结构生化性质。通过硅（分子对接）和体外（抗氧化（DPPH， ABTS）活性，抗炎症（RBC）， LDL和HDL修饰，硫代巴比妥物质，胆固醇外排试验和抗糖尿病）试验对新型类似物进行了深入研究，验证了α-淀粉酶抑制作用。酶抑制结果显示，化合物3d α-淀粉酶IC50值为1.79±0.12 μg，化合物3e α-淀粉酶IC50值为1.75±0.05 μg，标准药物阿卡波糖α-淀粉酶IC50值为1.53±0.20 μg。在这些新分子中，化合物3c和3d在硅和体外实验中表现出最高的抑制活性。研究表明，抑制剂3a-3j与人胰腺α-淀粉酶活性位点结合强烈，突出了它们作为有效抑制剂的潜力。这些研究结果有助于改善抗糖尿病药物先导分子的开发领域。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell Biochemistry and Biophysics 生物-生化与分子生物学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

7.5 months

期刊介绍： Cell Biochemistry and Biophysics (CBB) aims to publish papers on the nature of the biochemical and biophysical mechanisms underlying the structure, control and function of cellular systems The reports should be within the framework of modern biochemistry and chemistry, biophysics and cell physiology, physics and engineering, molecular and structural biology. The relationship between molecular structure and function under investigation is emphasized. Examples of subject areas that CBB publishes are: · biochemical and biophysical aspects of cell structure and function; · interactions of cells and their molecular/macromolecular constituents; · innovative developments in genetic and biomolecular engineering; · computer-based analysis of tissues, cells, cell networks, organelles, and molecular/macromolecular assemblies; · photometric, spectroscopic, microscopic, mechanical, and electrical methodologies/techniques in analytical cytology, cytometry and innovative instrument design For articles that focus on computational aspects, authors should be clear about which docking and molecular dynamics algorithms or software packages are being used as well as details on the system parameterization, simulations conditions etc. In addition, docking calculations (virtual screening, QSAR, etc.) should be validated either by experimental studies or one or more reliable theoretical cross-validation methods.