Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity
Twenty-one novel ester tethered artemisinin-isatin hybrids were designed, synthesized and screened against human myeloid leukemia cell lines (K562 and K562/ADR), human acute lymphoblastic leukemia cell line (CCRF-CEM) as well as normal human peripheral blood mononuclear cells (PBMCs) for their cytot...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-04-01
|
| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1112369/full |
| _version_ | 1797847192580390912 |
|---|---|
| author | Peng Wang Zhe Zhang Wei Cao Xuan Zhang |
| author_facet | Peng Wang Zhe Zhang Wei Cao Xuan Zhang |
| author_sort | Peng Wang |
| collection | DOAJ |
| description | Twenty-one novel ester tethered artemisinin-isatin hybrids were designed, synthesized and screened against human myeloid leukemia cell lines (K562 and K562/ADR), human acute lymphoblastic leukemia cell line (CCRF-CEM) as well as normal human peripheral blood mononuclear cells (PBMCs) for their cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships (SARs) were also discussed to facilitate further rational design of more effective candidates. The preliminary results showed that most of the ester tethered artemisinin-isatin hybrids (IC50: 0.32-29.35 µM) exhibited promising activity against CCRF-CEM cells, and some of them (IC50: 1.23-49.84 µM) were also active against K562 and K562/ADR human myeloid leukemia cell lines. Among them, hybrid 7d (IC50: 0.32, 2.67 and 1.23 µM) not only possessed profound activity against the three tested leukemia cell lines and excellent safety and selectivity profiles, but also showed promising pharmacokinetic properties. Accordingly, hybrid 7d could be considered as a potential lead molecule for the development of novel anti-leukemic agents with minimal untoward events to normal human cells. |
| first_indexed | 2024-04-09T18:07:20Z |
| format | Article |
| id | doaj.art-e99fb334d6fd4d57beeffcb21dfd53b6 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-09T18:07:20Z |
| publishDate | 2023-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-e99fb334d6fd4d57beeffcb21dfd53b62023-04-14T05:39:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-04-011310.3389/fonc.2023.11123691112369Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicityPeng Wang0Zhe Zhang1Wei Cao2Xuan Zhang3Department of Critical Care Unit, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Tumor Radiotherapy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaDepartment of Nephrology, The First Affiliated Hospital of Shandong First Medical University & Provincial Qianfoshan Hospital, Shandong Institute of Nephrology, Jinan, Shandong, ChinaDepartment of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, ChinaTwenty-one novel ester tethered artemisinin-isatin hybrids were designed, synthesized and screened against human myeloid leukemia cell lines (K562 and K562/ADR), human acute lymphoblastic leukemia cell line (CCRF-CEM) as well as normal human peripheral blood mononuclear cells (PBMCs) for their cytotoxicity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The structure-activity relationships (SARs) were also discussed to facilitate further rational design of more effective candidates. The preliminary results showed that most of the ester tethered artemisinin-isatin hybrids (IC50: 0.32-29.35 µM) exhibited promising activity against CCRF-CEM cells, and some of them (IC50: 1.23-49.84 µM) were also active against K562 and K562/ADR human myeloid leukemia cell lines. Among them, hybrid 7d (IC50: 0.32, 2.67 and 1.23 µM) not only possessed profound activity against the three tested leukemia cell lines and excellent safety and selectivity profiles, but also showed promising pharmacokinetic properties. Accordingly, hybrid 7d could be considered as a potential lead molecule for the development of novel anti-leukemic agents with minimal untoward events to normal human cells.https://www.frontiersin.org/articles/10.3389/fonc.2023.1112369/fullartemisininisatinhybrid moleculesanti-leukemic cytotoxicitystructure-activity relationship |
| spellingShingle | Peng Wang Zhe Zhang Wei Cao Xuan Zhang Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity Frontiers in Oncology artemisinin isatin hybrid molecules anti-leukemic cytotoxicity structure-activity relationship |
| title | Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity |
| title_full | Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity |
| title_fullStr | Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity |
| title_full_unstemmed | Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity |
| title_short | Development and evaluation of novel artemisinin-isatin hybrids with potential anti-leukemic cytotoxicity |
| title_sort | development and evaluation of novel artemisinin isatin hybrids with potential anti leukemic cytotoxicity |
| topic | artemisinin isatin hybrid molecules anti-leukemic cytotoxicity structure-activity relationship |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1112369/full |
| work_keys_str_mv | AT pengwang developmentandevaluationofnovelartemisininisatinhybridswithpotentialantileukemiccytotoxicity AT zhezhang developmentandevaluationofnovelartemisininisatinhybridswithpotentialantileukemiccytotoxicity AT weicao developmentandevaluationofnovelartemisininisatinhybridswithpotentialantileukemiccytotoxicity AT xuanzhang developmentandevaluationofnovelartemisininisatinhybridswithpotentialantileukemiccytotoxicity |