Alkaloids, styryl lactones, and acetogenin from the roots of Goniothalamus lanceolatus Miq. and their antiproliferative activity / Nurulfazlina Edayah Rasol

Goniothalamus lanceolatus Miq., locally known as selukai or getimang is an ethnomedicinal plant indigenous to Sarawak. It is used traditionally to treat cancer. Phytochemical investigation on the roots of G. lanceolatus Miq. was conducted with the objective of comprehensively analyse the chemical constituents present in the roots of G lanceolatus, especially the ones potentially active as antiproliferative agents. The roots of G lanceolatus Miq. was extracted successively using hexane, dichloromethane, and methanol. The hexane and dichloromethane extracts showed antiproliferative activity against colorectal and lung cancer cell lines with percentage viability of cell less than 15%. Among the two extracts, the HPLC-DAD profile of the dichloromethane extract revealed the presence of more active UV components, and thus selected for further investigation. Mass-based dereplication strategy using inhouse and online mass database system successfully identified 24 constituents comprising of styryl lactones, alkaloids, and acetogenins in the dichloromethane extract. Isolation and purification from the active antiproliferative fractions, M2 to M7 led to characterization often styryl lactones, five alkaloids, and one acetogenin, where six dereplicated compounds were verified. All the structures were elucidated using 1Dand 2D-NMR spectroscopy. Absolute configurations of the styryl lactones were established by ECD analysis through comparison of the experimental and theoretically calculated ECD spectra, while stereochemistry of the alkaloids were established using the single X-ray crystallography data. The known 5-goniothalamin and parvistone D, are reported for the first time from Goniothalamus genus. Two new styryl lactones 57?,6i?-5-hydroxy-6-styryltetrahydropyrane-2-one and goniolanceolatin E, and five new styryl lactone diastereomers, 5i?,6i?-5-acetylgoniothalamin, 5R,6R-5- hydroxygoniothalamin, goniofupyrone B, deoxygoniopypyrone B, and goniolanceolatin A, along with a known pyrano-pyrone, lS,5S,7R,8S,3-exo,7-endo- (+)-8-ep/-9-deoxygoniopypyrone are described. The 6S/IS- styryl lactones isolated in this work are new discoveries in Goniothalamus species. Biogenesis pathway of these 6S/IS styryl lactones are proposed. In addition, two new alkaloids, (-)- goniolanceolactam and 2-acetyl-3-amino-1,4-naphthoquinone were also identified along with the known alkaloids, 2-acetyl-3-amino-5-hydroxy-1,4-naphthoquinone, cleistopholine and liriodenine, and the acetogenin, annonacin. 5-Goniothalamin, (-)- goniolanceolactam and annonacin exhibited potential antiproliferative activity against all tested cancer cell lines with the IC50 values of less than 10.0 |uM. The alkaloids, 2- acetyl-3 -amino-1,4-naphthoquinone and 2-acetyl-3 -amino-5-hydroxy-1,4- naphthoquinone, as well as liriodenine demonstrated antiproliferative against HCT116, A549, and NCI-H23 cell lines with IC50 values ranging between 4.5 to 10.3 |uM. 5i?,6i?- 5-hydroxygoniothalamin showed selective activity against lung cancer cell lines, A549, and NCI-H1299, with the IC50 values of 8.0 and 8.9 \*M, respectively. Other styryl lactones exhibited only weak activity. All isolated compounds were non-toxic to normal cell lines except for annonacin

Chemical constituents of the leaves of Actinodaphne pruinosa

ABSTRACT. This study was designed to investigate the chemical constituents from Actinodaphne pruinosa growing in Malaysia. A phytochemical investigation of the leaves part resulted in the isolation of boldine (1), norboldine (2), laurotetanine (3), reticuline (4), syringaresinol (5), lupeol (6), and taraxerol (7). The structures of the isolated phytochemicals were established by analysis of their spectroscopic data, as well as the comparison with that of reported data. Notably, this is the first time to report the isolation and structural elucidation of the constituents from the leaves part of A. pruinosa.   KEY WORDS: Actinodaphne pruinosa, Aporphine, Lauraceae, Phytochemical   Bull. Chem. Soc. Ethiop. 2022, 36(4), 963-969.                                                               DOI: https://dx.doi.org/10.4314/bcse.v36i4.2

Acute oral toxicity study of root methanol extract of Goniothalamus lanceolatus miq. and its isolated bioactive compound (parvistone D) in murine model

Goniothalamus lanceolatus Miq. is widely used by the indigenous people of Sarawak, Malaysia as a folk remedy to treat various ailments including skin diseases, cold, and fever. A previous study reported that the root methanol extract, and parvistone D, an active compound of the plant, showed promising in vitro antiplasmodial activity against Plasmodium parasites. However, there is limited data reporting on its toxicological profile. Thus, this study aims to evaluate the potential toxicity of root methanol extract and parvistone D of G. lanceolatus in mice. The acute oral toxicity of the extract and compound was assessed at a single dose of 2000 and 500 mg/kg body weight, respectively. The animals were observed for any mortality, behavioral, motor-neuronal abnormalities, and body weight changes for 14 days. At the end of the experiment, relative organ weights were measured, and gross examination, as well as histopathological analysis, were performed. There was no sign of toxicity, and mortality seen in mice treated with G. lanceolatus root methanol extract, and parvistone D at the administered doses. In addition, no significant differences were observed in the body and relative organ weights between the control and treated groups. Gross and histopathological examinations showed normal appearance of the liver, spleen, kidneys, heart, and lungs as compared to their respective control groups. In conclusion, oral administration of root methanol extract, and parvistone D of G. lanceolatus are safe at the studied dosage levels and cause no acute toxicity in mice

Subchronic toxicity, immunoregulation and anti-breast tumor effect of Nordamnacantal, an anthraquinone extracted from the stems of Morinda citrifolia L.

Background: Morinda citrifolia L. that was reported with immunomodulating and cytotoxic effects has been traditionally used to treat multiple illnesses including cancer. An anthraquinone derived from fruits of Morinda citrifolia L., nordamnacanthal, is a promising agent possessing several in vitro biological activities. However, the in vivo anti-tumor effects and the safety profile of nordamnacanthal are yet to be evaluated. Methods: In vitro cytotoxicity of nordamnacanthal was tested using MTT, cell cycle and Annexin V/PI assays on human MCF-7 and MDA-MB231 breast cancer cells. Mice were orally fed with nordamnacanthal daily for 28 days for oral subchronic toxicity study. Then, the in vivo anti-tumor effect was evaluated on 4T1 murine cancer cells-challenged mice. Changes of tumor size and immune parameters were evaluated on the untreated and nordamnacanthal treated mice. Results: Nordamnacanthal was found to possess cytotoxic effects on MDA-MB231, MCF-7 and 4T1 cells in vitro. Moreover, based on the cell cycle and Annexin V results, nordamnacanthal managed to induce cell death in both MDA-MB231 and MCF-7 cells. Additionally, no mortality, signs of toxicity and changes of serum liver profile were observed in nordamnacanthal treated mice in the subchronic toxicity study. Furthermore, 50 mg/kg body weight of nordamncanthal successfully delayed the progression of 4T1 tumors in Balb/C mice after 28 days of treatment. Treatment with nordamnacanthal was also able to increase tumor immunity as evidenced by the immunophenotyping of the spleen and YAC-1 cytotoxicity assays. Conclusion: Nordamnacanthal managed to inhibit the growth and induce cell death in MDA-MB231 and MCF-7 cell lines in vitro and cease the tumor progression of 4T1 cells in vivo. Overall, nordamnacanthal holds interesting anti-cancer properties that can be further explored

Annotation and Identification of Phytochemicals from <i>Eleusine indica</i> Using High-Performance Liquid Chromatography Tandem Mass Spectrometry: Databases-Driven Approach

Eleusine indica (L.) Gaertn is a perennial herb belonging to the Poaceae family. As the only species of Eleusine found abundantly in Malaysia, it is locally known as “rumput sambau” and has been traditionally used to treat various ailments including pain relief from vaginal bleeding, hastening the placenta delivery after childbirth, asthma, hemorrhoids, urinary infection, fever, and as a tonic for flu-related symptoms. A diverse array of biological activities have been reported for the plant, such as antimicrobial, cytotoxic, anticonvulsant, anti-inflammatory, analgesic, antipyretic, and hepatoprotective action. Despite many reports on its traditional uses and biological activities, limited chemical databases are available for the plant. Thus, the aims of this study were to annotate and identify the phytochemical constituents in the methanolic extract of E. indica through tandem LCMS-based analysis techniques using MZmine, GNPS, Compound Discoverer, and SIRIUS platforms. This technique managed to identify a total of 65 phytochemicals in the extract, comprising primary and secondary metabolites, and was verified by the isolation of one of the identified phytochemicals. The structural elucidation mainly using 1D and 2D NMR as well as comparison with values in the literature confirms the isolated phytochemical to be a 3-OH anomer of loliolide, a benzofuran-type of compound, which consequently increases the level of confidence in the applied technique. The research describes a useful method for the fast and simultaneous identification of phytochemicals in E. indica, contributing to the study of the chemical properties of the genus and family

Styryl Lactones from Roots and Barks Goniothalamus lanceolatus

A new styryl lactone, 5R,6R-5-hydroxy-6-styryltetrahydropyrane-2-one 2 was isolated from the roots of an endemic Goniothalamus lanceolatus Miq. of Sarawak, Malaysia. Furthermore, seven previously undescribed diastereomers, 5R,6R-5-hydroxygoniothalamin 3, 5R,6R-5-acetylgoniothalamin 4, 6S,7S,8Sgoniodiol-7-monoacetate 5, 6S,7S,8S-goniodiol-8-monoacetate 6, goniofupyrone B 7, deoxygoniopypyrone B 8 and 1S,5S,7R,8S,3-endo,7-endo-(+)-8-epi-9- deoxygoniopypyrone acetate 9, along with six known styryl lactones (1, 10-15) were also isolated and characterized. 6S-goniothalamin 1 is reported for the first time from a Goniothalamus species. 1, 11 and 12 showed cytotoxic activity against human colon and lung cancer cell lines with IC50 values ranging from 2.38-7.59 µ

Styryl lactones from roots and barks goniothalamus lanceolatus

A new styryl lactone, 5R,6R-5-hydroxy-6-styryltetrahydropyrane-2-one 2 was isolated from the roots of an endemic Goniothalamus lanceolatus Miq. of Sarawak, Malaysia. Furthermore, seven previously undescribed diastereomers, 5R,6R-5-hydroxygoniothalamin 3, 5R,6R-5-acetylgoniothalamin 4, 6S,7S,8S-goniodiol-7-monoacetate 5, 6S,7S,8S-goniodiol-8-monoacetate 6, goniofupyrone B 7, deoxygoniopypyrone B 8 and 1S,5S,7R,8S,3-endo,7-endo-(+)-8-epi-9-deoxygoniopypyrone acetate 9, along with six known styryl lactones (1, 10-15) were also isolated and characterized. 6S-goniothalamin 1 is reported for the first time from a Goniothalamus species. 1, 11 and 12 showed cytotoxic activity against human colon and lung cancer cell lines with IC 50 values ranging from 2.38-7.59 µM

Cytotoxic lactam and naphthoquinone alkaloids from roots of Goniothalamus lanceolatus Miq.

Two new alkaloids, (−)-goniolanceolactam (1) and 2-acetyl-3-amino-1,4-naphthoquinone (2), along with two known naphthoquinone alkaloids, 2-acetyl-3-amino-5-hydroxy-1,4-naphthoquinone (3) and cleistopholine (4) were isolated from the cytotoxic, dichloromethane root extract of Goniothalamus lanceolatus (Annonaceae). The structures were elucidated by spectroscopic techniques and the absolute configuration of 1 was established by single-crystal X-ray diffraction. Alkaloid 1 showed cytotoxic activity on human colon and lung cancer cell lines with IC50 values ranging from 5.32 to 9.91 μM. © 2018 Phytochemical Society of Europ

Isolation and Characterization of Compounds from Ochreinauclea maingayi (Hook. f.) Ridsd. (Rubiaceae) with the Aid of LCMS/MS Molecular Networking

Phytochemical investigation of the dichloromethane crude extract from the bark of Ochreinauclea maingayi with the aid of LCMS/MS-based molecular networking guided the isolation and accelerated the elucidation of known and new indole alkaloids. The molecular networking analysis produces two main clusters, along with 41 non-prioritized clusters and self-loop nodes. Each cluster has several nodes which depict the fractions contained within those nodes. An implementation of a fraction mapping for each node represents the molecular weight and key fragment data of each compound. From the analysis of each cluster and node, we can deduce the indole alkaloids are the scaffold of interest. Indole scaffold can be found between F5 and F10 that contain several types of indole alkaloids. In total, we have successfully purified nine indole alkaloids, including 9H-&beta;-carboline-4-carboxylate 2, norharmane 3, harmane 4, naucledine 10, neonaucline 15, 1,2,3,4-tetranorharmane-1-one 16, naulafine 19, cadambine 9, and a new monoterpene indole alkaloid dihyrodeglycocadambine 7 from F5 to F10 using a chromatographic technique. Their structures were confirmed by 1D-NMR, 2D-NMR, UV, IR, LCMS, and MS2LDA. Several clusters and nodes contain ions that could not be annotated, suggesting that they may possess novel compounds that are yet to be discovered

Phytoconstituents of <i>Endiandra kingiana</i>; antidiabetic effects and molecular docking studies on alpha-amylase and alpha-glucosidase

Phytochemical investigation on the bark of E. kingiana plant afforded ten compounds, including six polyketides namely kingianin A 1, kingianin B 2, kingianin E 3, kingianin F 4, kingianin K 5 and kingianin L 6, three endiandric acids; kingianic acid A 7, tsangibeilin B 8 and endiandric acid M 9, and one sesquiterpene; daibuoxide 10. All compounds were separated as racemic mixture by recycling high-performance liquid chromatography (RHPLC), except for daibuoxide. Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. This is the first report on the presence of the sesquiterpene; daibuoxide in Endiandra genus. In vitro enzymatic bio-evaluation of the isolated compounds against α-amylase and α-glucosidase showed that 4 demonstrated the best α-amylase and α-glucosidase inhibitory activity with IC50 values of 181.54 ± 6.27 µg/mL and 237.87 ± 0.07 µg/mL, respectively. In addition, molecular docking analysis confirmed the α-amylase and α-glucosidase inhibitory activities demonstrated by 4.</p