Rafat M. Mohareb, Ibram Refat Mikhail, Marwa Soliman Gamaan, Ensaf S. Alwan
{"title":"噻吩并[3,2-e]吲唑衍生物的合成、抗增殖评价和分子对接","authors":"Rafat M. Mohareb, Ibram Refat Mikhail, Marwa Soliman Gamaan, Ensaf S. Alwan","doi":"10.2174/0115701808287763240302165049","DOIUrl":null,"url":null,"abstract":"Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications. Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents. Method: The 2-aryllidenecyclohexane-1,3-dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds. Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31mM. Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.","PeriodicalId":18059,"journal":{"name":"Letters in Drug Design & Discovery","volume":null,"pages":null},"PeriodicalIF":1.2000,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives\",\"authors\":\"Rafat M. Mohareb, Ibram Refat Mikhail, Marwa Soliman Gamaan, Ensaf S. Alwan\",\"doi\":\"10.2174/0115701808287763240302165049\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications. Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents. Method: The 2-aryllidenecyclohexane-1,3-dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds. Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31mM. Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.\",\"PeriodicalId\":18059,\"journal\":{\"name\":\"Letters in Drug Design & Discovery\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.2000,\"publicationDate\":\"2024-04-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Letters in Drug Design & Discovery\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/0115701808287763240302165049\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Letters in Drug Design & Discovery","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0115701808287763240302165049","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Synthesis, Antiproliferative Evaluation, and Molecular Docking of Thieno[3,2-e]indazole Derivatives
Background: Although indazole derivatives are rare and may not be available easily in nature, there are many reports demonstrating their pharmaceutical and other applications. Objective: This study aimed to synthesize new indazole derivatives and evaluate their antiproliferative activity to produce new anti-cancer agents. Method: The 2-aryllidenecyclohexane-1,3-dione derivatives 3a-c were obtained through the reaction of cyclohexane-1,3-dione with aromatic aldehydes used for the synthesis of thieno-[3,2-e]indazole derivatives. These derivatives were characterized by extensive analytical and spectral studies and were further used as starting materials for some heterocyclic transformations to produce biologically active compounds. The antiproliferative activities of the newly synthesized compounds were evaluated against the six cancer cell lines, A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460. Most of the tested compounds exhibited high cytotoxicity except a few compounds. Results: In this study, new compounds were synthesized, characterized, and evaluated toward the selected six cancer cell lines. All tested compounds displayed potent c-Met enzymatic activity with IC50 values ranging from 0.25 to 10.30 nM and potent prostate PC-3 cell line inhibition with IC50 values ranging from 0.17 to 9.31mM. Conclusion: The results obtained in this work demonstrated that the variations in substituents within the aryl moiety, together with the attached heterocyclic ring, have a notable influence on the antiproliferative activity. The results obtained in this work encourage further work in the future.
期刊介绍:
Aims & Scope
Letters in Drug Design & Discovery publishes letters, mini-reviews, highlights and guest edited thematic issues in all areas of rational drug design and discovery including medicinal chemistry, in-silico drug design, combinatorial chemistry, high-throughput screening, drug targets, and structure-activity relationships. The emphasis is on publishing quality papers very rapidly by taking full advantage of latest Internet technology for both submission and review of manuscripts. The online journal is an essential reading to all pharmaceutical scientists involved in research in drug design and discovery.