{"title":"新型2-羟基苯乙酮衍生物抗hiv -1药物的设计、合成、对接研究和生物学评价。","authors":"Samira Sooreni Oliaie, Mahdieh Safakish, Rouhollah Vahabpour Roudsari, Mohammad Mahboubi-Rabbani, Zahra Hajimahdi, Afshin Zarghi","doi":"10.2174/011570162X261377231107110447","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.</p><p><strong>Objective: </strong>The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.</p><p><strong>Methods: </strong>A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).</p><p><strong>Results: </strong>Most of the synthesized analogs were found to be moderately active against the virus, with EC<sub>50</sub> values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC<sub>50</sub> > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC<sub>50</sub> values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg<sup>2+</sup> coordination might be the possible mechanism of the anti-viral activity.</p><p><strong>Conclusion: </strong>Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.</p>","PeriodicalId":10911,"journal":{"name":"Current HIV Research","volume":" ","pages":"290-300"},"PeriodicalIF":0.8000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, Synthesis, Docking Studies, and Biological Evaluation of Novel 2-Hydroxyacetophenone Derivatives as Anti-HIV-1 Agents.\",\"authors\":\"Samira Sooreni Oliaie, Mahdieh Safakish, Rouhollah Vahabpour Roudsari, Mohammad Mahboubi-Rabbani, Zahra Hajimahdi, Afshin Zarghi\",\"doi\":\"10.2174/011570162X261377231107110447\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.</p><p><strong>Objective: </strong>The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.</p><p><strong>Methods: </strong>A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).</p><p><strong>Results: </strong>Most of the synthesized analogs were found to be moderately active against the virus, with EC<sub>50</sub> values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC<sub>50</sub> > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC<sub>50</sub> values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg<sup>2+</sup> coordination might be the possible mechanism of the anti-viral activity.</p><p><strong>Conclusion: </strong>Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.</p>\",\"PeriodicalId\":10911,\"journal\":{\"name\":\"Current HIV Research\",\"volume\":\" \",\"pages\":\"290-300\"},\"PeriodicalIF\":0.8000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Current HIV Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2174/011570162X261377231107110447\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current HIV Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/011570162X261377231107110447","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Design, Synthesis, Docking Studies, and Biological Evaluation of Novel 2-Hydroxyacetophenone Derivatives as Anti-HIV-1 Agents.
Background: The persistence of HIV mutations and the existence of multidrug resistance have produced an opportunity for an array of innovative anti-HIV medicines with a variety of structures that target HIV key enzymes.
Objective: The goal of this work was to find a new class of anti-HIV drugs founded on HIV integrase inhibitor pharmacophores.
Methods: A novel class of 2-hydroxy acetophenone analogs featuring substituted benzamide or N-phenylthiourea groups was designed and synthesized based on the general pharmacophore of HIV-1 integrase inhibitors (INs).
Results: Most of the synthesized analogs were found to be moderately active against the virus, with EC50 values ranging from 40 to 140 μM. Additionally, it was found that most of the compounds presented no considerable cytotoxicity (CC50 > 500 μΜ). The most potent compounds substituting with 4-fluorobenzamide (compound 7) and 4-methylbenzamide (compound 9) rings inhibited the HIV-1 replication by EC50 values of 40 and 45 μΜ, respectively. Docking studies using the crystallographic data available for PFV IN indicated that the Mg2+ coordination might be the possible mechanism of the anti-viral activity.
Conclusion: Our findings proved that the synthesized analogs may suggest a very good basis for the development of new anti-HIV-1 agents.
期刊介绍：
Current HIV Research covers all the latest and outstanding developments of HIV research by publishing original research, review articles and guest edited thematic issues. The novel pioneering work in the basic and clinical fields on all areas of HIV research covers: virus replication and gene expression, HIV assembly, virus-cell interaction, viral pathogenesis, epidemiology and transmission, anti-retroviral therapy and adherence, drug discovery, the latest developments in HIV/AIDS vaccines and animal models, mechanisms and interactions with AIDS related diseases, social and public health issues related to HIV disease, and prevention of viral infection. Periodically, the journal invites guest editors to devote an issue on a particular area of HIV research of great interest that increases our understanding of the virus and its complex interaction with the host.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
