Nurul Alam Inayatsyah, Mohamad Jemain Mohamad Ridhwan, Alim Alsukor Aznirulhisham, Nurulfazlina Edayah Rasol, Noraini Kasim, Syahrul Imran
{"title":"作为潜在 α 葡萄糖苷酶抑制剂的新型山梨素磺酰胺衍生物的合成及其分子对接研究","authors":"Nurul Alam Inayatsyah, Mohamad Jemain Mohamad Ridhwan, Alim Alsukor Aznirulhisham, Nurulfazlina Edayah Rasol, Noraini Kasim, Syahrul Imran","doi":"10.1111/cbdd.14614","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. <i>α</i>-Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible <i>α-</i>glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (<b>1–16</b>). Findings suggested that all compounds have better <i>α-</i>glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1-deoxynojirimycin (334.90 ± 1.10 μM), with IC<sub>50</sub> values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound <b>13</b>, a trichloro phenyl substituted compound, with IC<sub>50</sub> value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound <b>13</b> established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency.</p>\n </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"104 3","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis of Novel Soritin Sulfonamide Derivatives as Potential α-Glucosidase Inhibitor and Their Molecular Docking Studies\",\"authors\":\"Nurul Alam Inayatsyah, Mohamad Jemain Mohamad Ridhwan, Alim Alsukor Aznirulhisham, Nurulfazlina Edayah Rasol, Noraini Kasim, Syahrul Imran\",\"doi\":\"10.1111/cbdd.14614\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. <i>α</i>-Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible <i>α-</i>glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (<b>1–16</b>). Findings suggested that all compounds have better <i>α-</i>glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1-deoxynojirimycin (334.90 ± 1.10 μM), with IC<sub>50</sub> values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound <b>13</b>, a trichloro phenyl substituted compound, with IC<sub>50</sub> value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound <b>13</b> established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency.</p>\\n </div>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":\"104 3\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.14614\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.14614","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis of Novel Soritin Sulfonamide Derivatives as Potential α-Glucosidase Inhibitor and Their Molecular Docking Studies
Diabetes Mellitus (DM) is linked to various factors causing cardiovascular diseases, with uncontrolled postprandial hyperglycemia being a direct contributor. α-Glucosidase inhibitors (AGIs) aid in reducing postprandial hyperglycemia, potentially mitigating cardiovascular risks. In order to synthesize novel chemical scaffolds with possible α-glucosidase inhibition activity, a series of novel soritin sulfonamide derivatives were synthesized. The soritin hydrazide was treated with various aryl sulfonyl chlorides to obtain targeted compounds (1–16). Findings suggested that all compounds have better α-glucosidase inhibition compared to standard drugs, acarbose (2187.00 ± 1.25 μM) and 1-deoxynojirimycin (334.90 ± 1.10 μM), with IC50 values ranging from 3.81 ± 1.67 μM to 265.40 ± 1.58 μM. The most potent analog was Compound 13, a trichloro phenyl substituted compound, with IC50 value of 3.81 ± 1.67 μM. Structure–activity relationship (SAR) showed that introducing an additional chlorine group into the parent nucleus increases the potency. The docking studies validated that Compound 13 established hydrogen bonds with the active site residues Asp214, Glu276, and Asp349, while being further stabilized by hydrophobic interactions, providing an explanation for its high potency.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.