{"title":"针对高淀粉酶血症的萘醌融合二氮杂卓:糖尿病和癌症的潜在治疗药物。","authors":"Sandhya Chahal, Payal Rani, Rajvir Singh, Gaurav Joshi, Roshan Kumar, Parvin Kumar, Deepak Wadhwa, Devender Singh, Jayant Sindhu","doi":"10.1080/17568919.2024.2400968","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.<b>Materials & methods:</b> Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established <i>via</i> preliminary screening against A549 based lung cancer cell line at 5 μM.<b>Results & conclusion:</b> Compound <b>4b</b> exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC<sub>50</sub> against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound <b>4p</b> has been selected for further studies, as it demonstrated significant cytotoxicity, while compound <b>4b</b> showed no effect on <i>AKT</i> gene expression but upregulated <i>IGF-1R</i> gene expression, suggesting a role in managing diabetes. Compound <b>4p</b> exhibited the ability to decrease <i>AKT</i> expression and increase <i>IGF-1R</i> expression, indicating its potential for treating both diabetes and cancer.</p>","PeriodicalId":12475,"journal":{"name":"Future medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Naphthoquinone fused diazepines targeting hyperamylasemia: potential therapeutic agents for diabetes and cancer.\",\"authors\":\"Sandhya Chahal, Payal Rani, Rajvir Singh, Gaurav Joshi, Roshan Kumar, Parvin Kumar, Deepak Wadhwa, Devender Singh, Jayant Sindhu\",\"doi\":\"10.1080/17568919.2024.2400968\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Aim:</b> Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.<b>Materials & methods:</b> Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established <i>via</i> preliminary screening against A549 based lung cancer cell line at 5 μM.<b>Results & conclusion:</b> Compound <b>4b</b> exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC<sub>50</sub> against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound <b>4p</b> has been selected for further studies, as it demonstrated significant cytotoxicity, while compound <b>4b</b> showed no effect on <i>AKT</i> gene expression but upregulated <i>IGF-1R</i> gene expression, suggesting a role in managing diabetes. Compound <b>4p</b> exhibited the ability to decrease <i>AKT</i> expression and increase <i>IGF-1R</i> expression, indicating its potential for treating both diabetes and cancer.</p>\",\"PeriodicalId\":12475,\"journal\":{\"name\":\"Future medicinal chemistry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-09-20\",\"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/10.1080/17568919.2024.2400968\",\"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/10.1080/17568919.2024.2400968","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Naphthoquinone fused diazepines targeting hyperamylasemia: potential therapeutic agents for diabetes and cancer.
Aim: Elevated levels of amylase in the blood, known as hyperamylasemia, have been correlated with diabetes and cancer. To investigate the impact of hyperamylasemia on cellular proliferation, it is imperative to design dual inhibitors targeting both α-amylase activity and cancer progression.Materials & methods: Naphthoquinone fused diazepines have been synthesized using multicomponent reaction with high Eco-score of 87 and evaluated for bio efficacy using antioxidant and α-amylase inhibition assay. A correlation between diabetes and cancer has been established via preliminary screening against A549 based lung cancer cell line at 5 μM.Results & conclusion: Compound 4b exhibited superior anti-oxidant and α-amylase inhibitory potential over butylated hydroxytoluene (BHT) and acarbose, respectively with uncompetitive mode of inhibition. Compounds possessing more than 50 % inhibition were then investigated for their IC50 against A549 (Lung cancer), and Breast cancer (MCF-7 and MDA-MB-231) cells. Among all, compound 4p has been selected for further studies, as it demonstrated significant cytotoxicity, while compound 4b showed no effect on AKT gene expression but upregulated IGF-1R gene expression, suggesting a role in managing diabetes. Compound 4p exhibited the ability to decrease AKT expression and increase IGF-1R expression, indicating its potential for treating both diabetes and cancer.
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.