Asif Ahmad, Uzma Salar, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Khalid Mohammed Khan, Farzana Shaheen
{"title":"胡椒醛衍生的希夫碱分子作为治疗阿尔茨海默病和糖尿病的潜在多靶点药物。","authors":"Asif Ahmad, Uzma Salar, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Khalid Mohammed Khan, Farzana Shaheen","doi":"10.1080/17568919.2025.2549677","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The dual burden of diabetes and Alzheimer's highlights the urgent need for multifunctional therapeutic agents. This study explores piperonal-derived Schiff base derivatives as potential dual-action enzyme inhibitors against <i>α</i>-amylase (AA), <i>α</i>-glucosidase (AG), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offers a promising strategy for managing both conditions.</p><p><strong>Methods: </strong>Schiff base derivatives of piperonal (heliotropin) were synthesized, structurally characterized, and explored against established drug targets of diabetes mellitus (DM) and Alzheimer's disease (AD).</p><p><strong>Results: </strong>Compounds <b>7</b> (IC<sub>50</sub> = 5.73 ± 0.01; 3.52 ± 0.02 <i>µ</i>M) and <b>17</b> (IC<sub>50</sub> = 10.91 ± 0.02; 7.38 ± 0.02 <i>µ</i>M) showed potent inhibitory effects against AG and AA enzymes, in comparison to acarbose (IC<sub>50</sub> = 14.98 ± 0.02 <i>µ</i>M; 14.64 ± 0.02 <i>µ</i>M). However, analogs <b>7</b>, <b>9</b>, <b>10</b>, <b>14</b>, and <b>15</b>, compounds <b>7</b> (IC<sub>50</sub> = 2.92 ± 0.02; 3.34 ± 0.02 <i>µ</i>M) and <b>9</b> (IC<sub>50</sub> = 8.16 ± 0.03; 7.19 ± 0.03 <i>µ</i>M) showed remarkable inhibitory results against AChE and BChE, respectively, compared to standard donepezil chloride (IC<sub>50</sub> = 37.89 ± 0.02 <i>µ</i>M; 41.56 ± 0.03 <i>µ</i>M). Comprehensive kinetic analyses and molecular docking supported findings by <i>in</i> <i>vitro</i> studies. Synthesized derivatives were also checked for their antioxidant potential and demonstrated significant activity.</p><p><strong>Conclusion: </strong>These complementary studies highlight several hit candidates for further development as therapeutic agents against DM and AD.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":"17 16","pages":"1959-1975"},"PeriodicalIF":3.4000,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408053/pdf/","citationCount":"0","resultStr":"{\"title\":\"Piperonal-derived Schiff base molecules as potential multi-target therapeutic agents against Alzheimer's and diabetes.\",\"authors\":\"Asif Ahmad, Uzma Salar, Musa Özil, Nimet Baltaş, Syeda Sumayya Tariq, Zaheer Ul-Haq, Khalid Mohammed Khan, Farzana Shaheen\",\"doi\":\"10.1080/17568919.2025.2549677\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The dual burden of diabetes and Alzheimer's highlights the urgent need for multifunctional therapeutic agents. This study explores piperonal-derived Schiff base derivatives as potential dual-action enzyme inhibitors against <i>α</i>-amylase (AA), <i>α</i>-glucosidase (AG), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offers a promising strategy for managing both conditions.</p><p><strong>Methods: </strong>Schiff base derivatives of piperonal (heliotropin) were synthesized, structurally characterized, and explored against established drug targets of diabetes mellitus (DM) and Alzheimer's disease (AD).</p><p><strong>Results: </strong>Compounds <b>7</b> (IC<sub>50</sub> = 5.73 ± 0.01; 3.52 ± 0.02 <i>µ</i>M) and <b>17</b> (IC<sub>50</sub> = 10.91 ± 0.02; 7.38 ± 0.02 <i>µ</i>M) showed potent inhibitory effects against AG and AA enzymes, in comparison to acarbose (IC<sub>50</sub> = 14.98 ± 0.02 <i>µ</i>M; 14.64 ± 0.02 <i>µ</i>M). However, analogs <b>7</b>, <b>9</b>, <b>10</b>, <b>14</b>, and <b>15</b>, compounds <b>7</b> (IC<sub>50</sub> = 2.92 ± 0.02; 3.34 ± 0.02 <i>µ</i>M) and <b>9</b> (IC<sub>50</sub> = 8.16 ± 0.03; 7.19 ± 0.03 <i>µ</i>M) showed remarkable inhibitory results against AChE and BChE, respectively, compared to standard donepezil chloride (IC<sub>50</sub> = 37.89 ± 0.02 <i>µ</i>M; 41.56 ± 0.03 <i>µ</i>M). Comprehensive kinetic analyses and molecular docking supported findings by <i>in</i> <i>vitro</i> studies. Synthesized derivatives were also checked for their antioxidant potential and demonstrated significant activity.</p><p><strong>Conclusion: </strong>These complementary studies highlight several hit candidates for further development as therapeutic agents against DM and AD.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":\"17 16\",\"pages\":\"1959-1975\"},\"PeriodicalIF\":3.4000,\"publicationDate\":\"2025-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12408053/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Future medicinal chemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17568919.2025.2549677\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/8/30 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future medicinal chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17568919.2025.2549677","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/8/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Piperonal-derived Schiff base molecules as potential multi-target therapeutic agents against Alzheimer's and diabetes.
Background: The dual burden of diabetes and Alzheimer's highlights the urgent need for multifunctional therapeutic agents. This study explores piperonal-derived Schiff base derivatives as potential dual-action enzyme inhibitors against α-amylase (AA), α-glucosidase (AG), acetylcholinesterase (AChE), and butyrylcholinesterase (BChE), offers a promising strategy for managing both conditions.
Methods: Schiff base derivatives of piperonal (heliotropin) were synthesized, structurally characterized, and explored against established drug targets of diabetes mellitus (DM) and Alzheimer's disease (AD).
Results: Compounds 7 (IC50 = 5.73 ± 0.01; 3.52 ± 0.02 µM) and 17 (IC50 = 10.91 ± 0.02; 7.38 ± 0.02 µM) showed potent inhibitory effects against AG and AA enzymes, in comparison to acarbose (IC50 = 14.98 ± 0.02 µM; 14.64 ± 0.02 µM). However, analogs 7, 9, 10, 14, and 15, compounds 7 (IC50 = 2.92 ± 0.02; 3.34 ± 0.02 µM) and 9 (IC50 = 8.16 ± 0.03; 7.19 ± 0.03 µM) showed remarkable inhibitory results against AChE and BChE, respectively, compared to standard donepezil chloride (IC50 = 37.89 ± 0.02 µM; 41.56 ± 0.03 µM). Comprehensive kinetic analyses and molecular docking supported findings by invitro studies. Synthesized derivatives were also checked for their antioxidant potential and demonstrated significant activity.
Conclusion: These complementary studies highlight several hit candidates for further development as therapeutic agents against DM and AD.
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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