Saqib Khan, Muhammad Yaqoob, Muhammad H H B Asad, Rafia Falak, Zaman Ashraf, Abdul Mannan, Syed M Bukhari, Fiaz Alam, Umer Rashid
{"title":"强效4-氨基苯磺酰胺衍生物抗蛇毒碱性磷酸酶（ALP）电位。","authors":"Saqib Khan, Muhammad Yaqoob, Muhammad H H B Asad, Rafia Falak, Zaman Ashraf, Abdul Mannan, Syed M Bukhari, Fiaz Alam, Umer Rashid","doi":"10.1080/17568919.2025.2561395","DOIUrl":null,"url":null,"abstract":"<p><strong>Aim: </strong><i>Naja oxiana</i> venom-induced alkaline phosphatase (ALP) enzyme has been documented for its detrimental effects post envenomation in the victims. Therefore, the present study was designed to evaluate the effectiveness of 4-aminobenzenesulfonamide-based derivatives against cobra venom-induced ALP enzyme.</p><p><strong>Methods: </strong>Targeted derivatives were synthesized and characterized via FTIR, <sup>1</sup>H NMR, and <sup>13</sup>C NMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potential to halt ALP activity.</p><p><strong>Results: </strong>Among all the synthetic compounds, (SB-5) showed remarkably potent inhibitory activity against the targeted enzyme (94%, IC<sub>50</sub>, 3.25 µM, <i>p</i> < 0.001). Furthermore, kinetic studies revealed that (SB-5) acts as a mixed-type inhibitor of ALP enzyme. Its Ki value (13.19 µM) indicated a high binding affinity, accompanied by a favorable safety profile - characterized by high gastrointestinal (GI) absorption, compliance with Lipinski's Rule of Five (0 violations), and a low likelihood of crossing the blood-brain barrier, suggesting good oral bioavailability. The Ramachandran plot offered further insight into the positioning of amino acid residues within the most favored regions, thereby reinforcing the potential to inhibit ALP activity.</p><p><strong>Conclusion: </strong>The present study confirms the effectiveness of 4-aminobenzenesulfonamide-based derivative (SB-5) as a promising inhibitor of ALP and as a lead candidate for future drug development.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":" ","pages":"1-11"},"PeriodicalIF":3.4000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Anti-alkaline phosphatases (ALP) potentials of potent 4-aminobenzenesulfonamide derivatives against <i>Naja oxiana</i> venom.\",\"authors\":\"Saqib Khan, Muhammad Yaqoob, Muhammad H H B Asad, Rafia Falak, Zaman Ashraf, Abdul Mannan, Syed M Bukhari, Fiaz Alam, Umer Rashid\",\"doi\":\"10.1080/17568919.2025.2561395\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aim: </strong><i>Naja oxiana</i> venom-induced alkaline phosphatase (ALP) enzyme has been documented for its detrimental effects post envenomation in the victims. Therefore, the present study was designed to evaluate the effectiveness of 4-aminobenzenesulfonamide-based derivatives against cobra venom-induced ALP enzyme.</p><p><strong>Methods: </strong>Targeted derivatives were synthesized and characterized via FTIR, <sup>1</sup>H NMR, and <sup>13</sup>C NMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potential to halt ALP activity.</p><p><strong>Results: </strong>Among all the synthetic compounds, (SB-5) showed remarkably potent inhibitory activity against the targeted enzyme (94%, IC<sub>50</sub>, 3.25 µM, <i>p</i> < 0.001). Furthermore, kinetic studies revealed that (SB-5) acts as a mixed-type inhibitor of ALP enzyme. Its Ki value (13.19 µM) indicated a high binding affinity, accompanied by a favorable safety profile - characterized by high gastrointestinal (GI) absorption, compliance with Lipinski's Rule of Five (0 violations), and a low likelihood of crossing the blood-brain barrier, suggesting good oral bioavailability. The Ramachandran plot offered further insight into the positioning of amino acid residues within the most favored regions, thereby reinforcing the potential to inhibit ALP activity.</p><p><strong>Conclusion: </strong>The present study confirms the effectiveness of 4-aminobenzenesulfonamide-based derivative (SB-5) as a promising inhibitor of ALP and as a lead candidate for future drug development.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":\" \",\"pages\":\"1-11\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17568919.2025.2561395\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2025.2561395","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Anti-alkaline phosphatases (ALP) potentials of potent 4-aminobenzenesulfonamide derivatives against Naja oxiana venom.
Aim: Naja oxiana venom-induced alkaline phosphatase (ALP) enzyme has been documented for its detrimental effects post envenomation in the victims. Therefore, the present study was designed to evaluate the effectiveness of 4-aminobenzenesulfonamide-based derivatives against cobra venom-induced ALP enzyme.
Methods: Targeted derivatives were synthesized and characterized via FTIR, 1H NMR, and 13C NMR followed by docking targeted protein techniques. Furthermore, synthetic analogues were evaluated in vitro for their potential to halt ALP activity.
Results: Among all the synthetic compounds, (SB-5) showed remarkably potent inhibitory activity against the targeted enzyme (94%, IC50, 3.25 µM, p < 0.001). Furthermore, kinetic studies revealed that (SB-5) acts as a mixed-type inhibitor of ALP enzyme. Its Ki value (13.19 µM) indicated a high binding affinity, accompanied by a favorable safety profile - characterized by high gastrointestinal (GI) absorption, compliance with Lipinski's Rule of Five (0 violations), and a low likelihood of crossing the blood-brain barrier, suggesting good oral bioavailability. The Ramachandran plot offered further insight into the positioning of amino acid residues within the most favored regions, thereby reinforcing the potential to inhibit ALP activity.
Conclusion: The present study confirms the effectiveness of 4-aminobenzenesulfonamide-based derivative (SB-5) as a promising inhibitor of ALP and as a lead candidate for future drug development.
期刊介绍：
Future Medicinal Chemistry offers a forum for the rapid publication of original research and critical reviews of the latest milestones in the field. Strong emphasis is placed on ensuring that the journal stimulates awareness of issues that are anticipated to play an increasingly central role in influencing the future direction of pharmaceutical chemistry. Where relevant, contributions are also actively encouraged on areas as diverse as biotechnology, enzymology, green chemistry, genomics, immunology, materials science, neglected diseases and orphan drugs, pharmacogenomics, proteomics and toxicology.
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