By the end of the twentieth century, the interest in natural compounds as probable sources of drugs has declined and was replaced by other strategies such as molecular target-based drug discovery. However, in the recent times, natural compounds regained their position as extremely important source drug leads. Indole-containing compounds are under clinical use which includes vinblastine and vincristine (anticancer), atevirdine (anti-HIV), yohimbine (erectile dysfunction), reserpine (antihypertension), ajmalicine (vascular disorders), ajmaline (anti-arrhythmic), vincamine (vasodilator), etc. Monoterpene Indole Alkaloids (MIAs) deserve the curiosity and attention of researchers due to their chemical diversity and biological activities. These compounds were considered as an impending source of drug-lead. In this review 444 compounds, were identified from six genera belonging to the family Apocynaceae, will be discussed. These genera (Alstonia, Rauvolfia, Kopsia, Ervatamia, and Tabernaemontana, and Rhazya) consist of 400 members and represent 20% of Apocynaceae species. Only 30 (7.5%) species were investigated, whereas the rest are promising to be investigated. Eleven bioactivities, including antibacterial, antifungal, anti-inflammatory and immunosuppressant activities, were reported. Whereas cytotoxic effect represents 47% of the reported activities. Convincingly, the genera selected in this review are a wealthy source for future anticancer drug lead.
: Rhazya stricta is a rich indole alkaloid medicinal plant species, that is used in traditional medicine particularly in Middle East countries to treat inflammations, diabetes, rheumatism, and skin disorders. The alkaloid plant extract of R. stricta was fractionated on aluminum oxide column and further purified by different chromatographic methods. The chemical structures of the isolated compounds were elucidated by interpretation of their 1D and 2D NMR, IR, UV and MS spectral data. The potential antitumor effect was examined against three cancer cell lines; HCT-116-colon cancer, PC-3-prostate cancer and HepG2-liver cancer as well as a control cell line (Vero) using MTT assay. Two new indole alkaloids, identified as 16-epi-stemmadenine-N-oxide (1) and stemmadenine-N-methyl (2), along with the known indole alkaloid 20-epi-antirhine (3) were isolated from the leaves of Rhazya stricta. Compound 2, stemmadenine-N-methyl exhibited a reasonable selectivity index and a broad anticancer effect against the examined cell lines with IC50 35.0±0.7, 35.0±0.6, 40.0±0.7and 79.0±1.0 μM, respectively. Furthermore, the effect of stemmadenine-N-methyl was evaluated on cell migration using woundhealing assay. It significantly hindered cell migration and delayed-wound healing. 16-epistemmadenine- N-oxide and stemmadenine-N-methyl are new indole alkaloids isolated from the leaves of Rhazya stricta, of which stemmadenine-N-methyl selectively inhibited the proliferation of three different cancer cell lines. In addition, it prevented cell migration and delayed wound-healing. Further studies are required to confirm the mechanism by which this promising alkaloid exhibits its antitumor activity.
Purification of the organic extract of Laurencia obtusa Lamouroux by column chromatography and preparative thin layer chromatography provided four new compounds: a eudesmane-type sesquiterpenoid [eudesma-4(15),11-diene-5,7-diol (1)], a cuparane-type sesquiterpenoid [10-hydroxycuparaldehyde (2)], and two nor-cuparanes [3-hydroxy-15-nor-cuparan-10β-ol (3) and 2-bromo-3-hydroxy-15-nor-cuparan-10β-ol (4)]. Structural identification was made possible by comparison of spectral data with those reported in the literature. Compounds 3 and 4 are significant as nor-cuparanes are rarely isolated from marine environment. 1 showed moderate anticandidal activity, whereas 2 exhibited reasonable antibacterial activity against multidrug-resistant bacteria (especially Gram-positive). All the compounds are nontoxic to Artemia salina.
Background: Rhazya stricta has been used as a folkloric medicinal herb for treating various diseases such as diabetes, inflammatory disorders, and sore throat. Several studies have revealed the potential of this plant as an important source of phytochemicals with anticancer properties. Objective: The present study was designed to isolate a novel anticancer compound from Rhazya stricta and elucidate its mechanism of action using genomics approach. Methods: Rhazya stricta leaves extract was prepared, and several alkaloids were purified and characterized. These alkaloids were screened for their anticancer potential. One of the alkaloids, termed as isopicrinine, showed efficient cytotoxicity against MCF7 breast cancer cell line and was selected for further analysis. RNA-Seq transcription profiling was conducted to identify the affected genes and cellular pathways in MCF7 cells after treatment with isopicrinine alkaloid. Results: In vitro studies revealed that newly identified isopicrinine alkaloid possess efficient anticancer activity. Exposure of MCF7 cells with isopicrinine affected the expression of various genes involved in p53 signaling pathway. One of the crucial proapoptotic genes, significantly upregulated in MCF7 after exposure to alkaloid, was PUMA (p53 upregulated modulator of apoptosis), which is involved in p53-dependent and -independent apoptosis. Moreover, exposure of sublethal dose of isopicrinine alkaloid in breast cancer cell line led to the downregulation of survivin, which is involved in negative regulation of apoptosis. Besides, several genes involved in mitosis and cell proliferation were significantly downregulated. Conclusion: In this article, we report the determination of a new alkaloid isopicrinine from the aerial parts of Rhazya stricta with anticancer property. This compound has the potential to be developed as a drug for curing cancer.
Chromatographic investigation of the aerial parts of the Rhazya stricta (Apocynaceae) resulted in the isolation of two new monoterpene indole alkaloids, 6-nor-antirhine-N1-methyl (1) and razyamide (2), along with six known compounds, eburenine (3), epi-rhazyaminine (4), rhazizine (5), 20-epi-sitsirikine (6), antirhine (7), and 16-epi-stemmadenine-N-oxide (8). The chemical structures were established by various spectroscopic experiments. Compounds 1–8 exhibited cytotoxic effects against three cancer cells with IC50 values ranging between 5.1 ± 0.10 and 93.2 ± 9.73 µM against MCF-7; 5.1 ± 0.28 and 290.2 ± 7.50 µM against HepG2, and 3.1 ± 0.17 and 55.7 ± 4.29 µM against HeLa cells. Compound 2 showed the most potent cytotoxic effect against all cancer cell lines (MCF-7, HepG2 and HeLa with IC50 values = 5.1 ± 0.10, 5.1 ± 0.28, and 3.1 ± 0.17 µM, respectively). Furthermore, compound 2 revealed a significant increase in the apoptotic cell population of MCF-7, HepG2, and HeLa cells, with 31.4 ± 0.2%, 29.2 ± 0.5%, and 34.9 ± 0.6%, respectively. Compound 2 decreased the percentage of the phagocytic pathway on HepG2 cells by 15.0 ± 0.1%. These findings can explain the antiproliferative effect of compound 2.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.