Leukemia is a blood or bone marrow cancer with increasing incidence in developed regions of the world. Currently, there is an ongoing need for novel and safe anti-leukemic agents, as no fully effective chemotherapy is available to treat this life-threatening disease. Herein, are reported the isolation, structural elucidation, and anti-leukemic evaluation of twenty-nine withanolide-type steroids (-) from . Among them, the new isolated withanolides, withaperoxidins A-D (-) have an unusual six-membered cyclic peroxide moiety on the withasteroid skeleton as a structural novelty. Their structures have been elucidated by means of spectroscopic analyses, including 2D NMR experiments. In addition, extensive structure-activity relationships and in silico ADME studies were employed to understand the pharmacophore and pharmacokinetic properties of this series of withasteroids. Compounds , , and together with withaferin A () were identified as having improved antiproliferative effect (IC ranging from 0.2 to 0.7 μM) on human leukemia HL-60 cell lines compared with the reference drug, etoposide. This cytotoxic potency was also coupled with good selectivity index (SI 33.0-9.2) on non-tumoral Vero cell line and in silico drug likeness. These findings revealed that these natural withasteroids are potential candidates as chemotherapeutic agents in the treatment of leukemia.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7731379 | PMC |
| http://dx.doi.org/10.3390/molecules25235744 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A systematic review of spirostanol saponins and anticancer natural products isolated from Tacca plantaginea (Hance) Drenth.
Phytochemistry
December 2024
University of Lille, CNRS, Inserm, CHU Lille, UMR9020 - UMR1277 - Canther - Cancer Heterogeneity, Plasticity and Resistance to Therapies, 59000, Lille, France; University of Lille, Faculty of Pharmacy, Institut de Chimie Pharmaceutique Albert Lespagnol (ICPAL), 3 rue du Professeur Laguesse, 59000, Lille, France; OncoWitan, Consulting Scientific Office, Lille, (Wasquehal), 59290, France. Electronic address:
The plant genus Tacca comprises twenty species including Tacca plantaginea, essentially distributed in the Indo-China region. Medicinal preparations from the rhizomes are used traditionally to treat gastrointestinal ailments, stomach aches and inflammatory disorders. A variety of bioactive molecules have been isolated from T.
View Article and Find Full Text PDFAnti-inflammatory withajardins from the leaves of Athenaea velutina.
Phytochemistry
November 2022
Departamento de Química Orgânica e Inorgânica, Centro de Ciências, Universidade Federal do Ceará, 60021-970, Fortaleza, CE, Brazil. Electronic address:
Withajardins, uncommon modified withanolide-type steroids, have been isolated exclusively from plants of the Solanaceae family so far. Two undescribed withajardins and the known tuboanosigenin were isolated from the hexane/EtOAc 1:1 extract from Athenaea velutina leaves. Their structures were established by an extensive analysis of 1D and 2D-NMR and HRMS data.
View Article and Find Full Text PDFOsteosarcoma cell proliferation suppression via SHP-2-mediated inactivation of the JAK/STAT3 pathway by tubocapsenolide A.
J Adv Res
December 2021
Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
Introduction: Previously, we have reported a withanolide-type steroid, named tubocapsenolide A (TA), which shows potent anti-proliferative activity in several cancer cell lines. However, its inhibitory effect on the Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway and therapeutic potential on osteosarcoma have not been reported.
Objectives: In the present study, we aimed to investigate the effect and molecular mechanism of TA in osteosarcoma.
Identification of HMGCR as the anticancer target of physapubenolide against melanoma cells by in silico target prediction.
Acta Pharmacol Sin
June 2022
Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.
Physapubenolide (PB), a withanolide-type compound extracted from the traditional herb Physalis minima L., has been demonstrated to exert remarkable cytotoxicity against cancer cells; however, its molecular mechanisms are still unclear. In this study, we demonstrated that PB inhibited cell proliferation and migration in melanoma cells by inducing cell apoptosis.
View Article and Find Full Text PDFWithanolide-Type Steroids from Inhibit HIV Transcription.
J Nat Prod
October 2021
Instituto Universitario de Bio-Orgánica Antonio González and Departamento de Química Orgánica, Universidad de La Laguna, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife Spain.
The aim of the present study is to report the isolation, structural elucidation, and antiviral evaluation of four new withanolide-type steroids, named nicansteroidins A-D (-), together with nine related known compounds (-) isolated from the aerial parts of . Their structures were established based on an extensive spectroscopic analysis, including 1D and 2D NMR techniques. Outstandingly, nicansteroidins A and B possess an unusual side chain with an exocyclic double bond on the δ-lactone system, whereas nicansteroidins C and D have an uncommon cycloperoxide functionality in ring A as distinct structural motifs.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!