Jelena Kesić, Mirjana Popsavin, Goran Benedeković, Vesna Kojić, Anita Bosak, Ana Matošević, Pavol Farkaš, Romana Madelová, Velimir Popsavin, Ivana Kovačević
{"title":"Synthesis and biological evaluation of natural cleistanolate, its enantiomer and analogues","authors":"Jelena Kesić, Mirjana Popsavin, Goran Benedeković, Vesna Kojić, Anita Bosak, Ana Matošević, Pavol Farkaš, Romana Madelová, Velimir Popsavin, Ivana Kovačević","doi":"10.1016/j.ejmech.2025.117326","DOIUrl":null,"url":null,"abstract":"Herein, the modified synthesis of natural lactone (−)-cleistanolate (<strong>1</strong>) and its enantiomer (<em>ent</em>-<strong>1</strong>), along with the synthesis of six new analogues (<strong>3</strong>, <strong>10</strong>, <strong>11</strong>, <strong>12</strong>, <strong>13</strong>, <em>ent</em>-<strong>3</strong>), is presented. The antiproliferative activity of natural product <strong>1</strong> and its 22 analogues with lactone moiety was evaluated <em>in vitro</em> against eight human tumour cell lines and one normal cell line. SAR analysis revealed structural characteristics important for the activity of these types of compounds. The synthesized analogues are completely inactive toward the normal MRC-5 cell line. Their selectivity indexes (SI) range from 2.98 to 891.64. Furthermore, antimicrobial potential and inhibition of human acetyl- and butyrylcholinesterases of <strong>1</strong> and selected compounds have been evaluated.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"89 1","pages":""},"PeriodicalIF":6.0000,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"European Journal of Medicinal Chemistry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ejmech.2025.117326","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
引用次数: 0
Abstract
Herein, the modified synthesis of natural lactone (−)-cleistanolate (1) and its enantiomer (ent-1), along with the synthesis of six new analogues (3, 10, 11, 12, 13, ent-3), is presented. The antiproliferative activity of natural product 1 and its 22 analogues with lactone moiety was evaluated in vitro against eight human tumour cell lines and one normal cell line. SAR analysis revealed structural characteristics important for the activity of these types of compounds. The synthesized analogues are completely inactive toward the normal MRC-5 cell line. Their selectivity indexes (SI) range from 2.98 to 891.64. Furthermore, antimicrobial potential and inhibition of human acetyl- and butyrylcholinesterases of 1 and selected compounds have been evaluated.
期刊介绍：
The European Journal of Medicinal Chemistry is a global journal that publishes studies on all aspects of medicinal chemistry. It provides a medium for publication of original papers and also welcomes critical review papers.
A typical paper would report on the organic synthesis, characterization and pharmacological evaluation of compounds. Other topics of interest are drug design, QSAR, molecular modeling, drug-receptor interactions, molecular aspects of drug metabolism, prodrug synthesis and drug targeting. The journal expects manuscripts to present the rational for a study, provide insight into the design of compounds or understanding of mechanism, or clarify the targets.
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