Abstract
Datura innoxia Mill., Solanaceae, an underexplored ethnomedicinal plant, has been empirically evaluated in the current study for the isolation of bioactive agents. A crude extract of D. innoxia leaves was subjected to normal-phase medium pressure and vacuum liquid chromatography which led to the purification of a withanolide, isowithametelin. The chemical structure was established based on single-crystal X-ray diffraction. Isowithametelin exhibited substantial cytotoxicity against tested human cancer cell lines (breast cancer MCF-7 (ATCC® HTB-22), lung carcinoma LU-1 (human lung carcinoma established in the Department of Surgical Oncology, University of Illinois at Chicago), and prostate adenocarcinoma PC-3 (ATCC® CRL-1435)) with IC50 values of 4.3 ± 0.93, 6.9 ± 1.3, and 0.01 ± 0.001 μg/ml, respectively. It also inhibited nitric oxide production in lipopolysaccharide-activated murine macrophage RAW 264.7 cells (IC50 value of 18.5 ± 1.8 μg/ml) and demonstrated moderate protein kinase inhibition. This work suggests a possible anticancer role of isowithametelin; in vivo studies remain necessary to corroborate in vitro efficacy.
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Acknowledgments
The authors are thankful to Prof. Dr. Rizwana Aleem Qureshi, Department of Plant Sciences, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan, for identifying the plant sample.
Funding
This work was supported by Higher Education Commission, Pakistan, under PhD indigenous fellowship program.
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HF performed the experiments and prepared the first draft of manuscript. MA helped in structure identification and proofread the manuscript. MWB helped in isolation studies. MNT performed crystallography. TPK and JMP performed and interpreted the results of cancer chemopreventive assays and proofread the manuscript. IH conceived, designed, and supervised the study.
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Fatima, H., Ahmed, M., Baig, M.W. et al. Cancer Chemopreventive and Cytotoxic Activities of Isowithametelin from Datura innoxia. Rev. Bras. Farmacogn. 30, 723–728 (2020). https://doi.org/10.1007/s43450-020-00102-9
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DOI: https://doi.org/10.1007/s43450-020-00102-9