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Fulltext Synthesis of new cytotoxic aminoanthraquinone derivatives via nucleophilic substitution reactions

Nor SM, Sukari MA, Azziz SS, Fah WC, Alimon H, Juhan SF

Molecules, 2013 Jul 08;18(7):8046-62.
PMID: 23884135 DOI: 10.3390/molecules18078046

Aminoanthraquinones were successfully synthesized via two reaction steps. 1,4-Dihydroxyanthraquinone (1) was first subjected to methylation, reduction and acylation to give an excellent yield of anthracene-1,4-dione (3), 1,4-dimethoxyanthracene-9,10-dione (5) and 9,10-dioxo-9,10-dihydroanthracene-1,4-diyl diacetate (7). Treatment of 1, 3, 5 and 7 with BuNH2 in the presence of PhI(OAc)2 as catalyst produced seven aminoanthraquinone derivatives 1a, b, 3a, and 5a-d. Amination of 3 and 5 afforded three new aminoanthraquinones, namely 2-(butylamino)anthracene-1,4-dione (3a), 2-(butylamino)anthracene-9,10-dione (5a) and 2,3-(dibutylamino)anthracene-9,10-dione (5b). All newly synthesised aminoanthraquinones were examined for their cytotoxic activity against MCF-7 (estrogen receptor positive human breast) and Hep-G2 (human hepatocellular liver carcinoma) cancer cells using MTT assay. Aminoanthraquinones 3a, 5a and 5b exhibited strong cytotoxicity towards both cancer cell lines (IC50 1.1-13.0 µg/mL).

Matched MeSH terms: MCF-7 Cells/drug effects
Induction of apoptosis by chalepin through phosphatidylserine externalisations and DNA fragmentation in breast cancer cells (MCF7)

Fakai MI, Abd Malek SN, Karsani SA

Life Sci, 2019 Mar 01;220:186-193.
PMID: 30682342 DOI: 10.1016/j.lfs.2019.01.029

AIMS: Chalepin, a naturally occurring compound isolated from Ruta angustifolia have been shown to exert a promising anticancer activity through various mechanisms. Hence, the need to investigate the apoptotic inducing ability of chalepin in MCF7 cells by various detection assays.
MATERIALS AND METHODS: Cytotoxicity screening of chalepin against MCF7 cells was conducted using SRB assay. Apoptosis induction was examined by established morphological and biochemical assays including phase contrast and Hoechst/PI staining fluorescence microscope. Similarly, Annexin-V/FITC and TUNEL assays were conducted using flow cytometry whereas caspase-3 activity was evaluated using microplate reader.
KEY FINDINGS: The result indicates remarkable cytotoxic activity against MCF7 cells, whereas it shows moderate cytotoxic activity against MDA-MB231 cells. Interestingly, chalepin did not present any toxicity against MRC5 normal cell line. Morphological examination using both phase contrast and fluorescence microscope displays typical apoptotic features such as membrane blebbing, DNA fragmentation, chromatin condensation and apoptotic bodies' formation following chalepin treatment against MCF7 cells at different concentration for 48 h. Apoptosis induction is significantly associated with externalisation of phosphatidylserine, and DNA fragmentation in MCF7 cells chalepin treated cells when compared with control. The protein expressions of caspase-8, 9 and cleaved PARP1 were upregulated which correlated well with increased caspase-3 activity.
SIGNIFICANCE: From our recent findings, chalepin was able to induced apoptosis in MCF7 cells and therefore, could be evaluated further as a potential source of anticancer agent for cancer treatment such as breast cancer.

Matched MeSH terms: MCF-7 Cells/drug effects
Cytotoxic and cell cycle arrest induction of pentacyclic triterpenoides separated from Lantana camara leaves against MCF-7 cell line in vitro

Shamsee ZR, Al-Saffar AZ, Al-Shanon AF, Al-Obaidi JR

Mol Biol Rep, 2019 Feb;46(1):381-390.
PMID: 30426385 DOI: 10.1007/s11033-018-4482-3

Lantana camara is an important medicinal plant that contains many active compounds, including pentacyclic triterpenoids, with numerous biological activities. The present study was conducted to evaluate the anti-oxidant, anti-tumour, and cell cycle arrest properties of chemical compounds extracted from L. camara leaves. Four compounds were identified after subjecting the plant methanolic extract to LC-MS/MS analysis: lantadene A, lantadene B, icterogenin, and lantadene C. Potential antioxidant activity was examined using 2, 2-diphenyl-1-picrylhydrazyl and compared with vitamin C as a control. Lantadene A and B were confirmed to possess the highest scavenging activity, while icterogenin and lantadene C exhibited a lesser antioxidant effect. All extracted compounds exerted a dose-dependent reduction in MCF-7 cell viability; however, lantadene B showed the highest anti-cancer activity, with an IC50 of 112.2 μg mL-1, and was therefore used in subsequent experiments. The results also confirmed the significant release of caspase 9 in a dose-dependent pattern following treatment of MCF-7 cells with a range of lantadene B concentrations. Lantadene B was found to induce MCF-7 cell cycle arrest in G1, blocking the G1/S transition with a maximum significant (p ≤ 0.01) cell count of 80.35% at 25 µg mL-1. No significant changes were observed in S phase, but a decrease in the MCF-7 population was exhibited in G2/M phase.

Matched MeSH terms: MCF-7 Cells/drug effects
Fulltext Development and Characterization of Calcium-Alginate Beads of Apigenin: In Vitro Antitumor, Antibacterial, and Antioxidant Activities

Aldawsari MF, Ahmed MM, Fatima F, Anwer MK, Katakam P, Khan A

Mar Drugs, 2021 Aug 20;19(8).
PMID: 34436306 DOI: 10.3390/md19080467

The objective of this work was to develop sustained-release Ca-alginate beads of apigenin using sodium alginate, a natural polysaccharide. Six batches were prepared by applying the ionotropic gelation technique, wherein calcium chloride was used as a crosslinking agent. The beads were evaluated for particle size, drug loading, percentage yield, and in vitro drug release. Particle size was found to decrease, and drug entrapment efficiency was enhanced with an increase in the polymer concentration. The dissolution study showed sustained drug release from the apigenin-loaded alginate beads with an increase in the polymer proportion. Based on the dissolution profiles, BD6 formulation was optimized and characterized for FTIR, DSC, XRD, and SEM, results of which indicated successful development of apigenin-loaded Ca alginate beads. MTT assay demonstrated a potential anticancer effect against the breast cancer MCF-7 cell lines. The antimicrobial activity exhibited effective inhibition in the bacterial and fungal growth rate. The DPPH measurement revealed that the formulation had substantial antioxidant activity, with EC50 value slightly lowered compared to pure apigenin. A stability study demonstrated that the BD6 was stable with similar (f2) drug release profiles in harsh condition. In conclusion, alginate-based beads could be used for sustaining the drug release of poorly water-soluble apigenin while also improving in vitro antitumor, antimicrobial, and antioxidant activity.

Matched MeSH terms: MCF-7 Cells/drug effects
Comparative nutritional and mycochemical contents, biological activities and LC/MS screening of tuber from new recipe cultivation technique with wild type tuber of tiger's milk mushroom of species Lignosus rhinocerus

Jamil NAM, Rashid NMN, Hamid MHA, Rahmad N, Al-Obaidi JR

World J Microbiol Biotechnol, 2017 Dec 04;34(1):1.
PMID: 29204733 DOI: 10.1007/s11274-017-2385-4

Tiger's milk mushroom is known for its valuable medicinal properties, especially the tuber part. However, wild tuber is very hard to obtain as it grows underground. This study first aimed to cultivate tiger's milk mushroom tuber through a cultivation technique, and second to compare nutritional and mycochemical contents, antioxidant and cytotoxic activities and compound screening of the cultivated tuber with the wild tuber. Results showed an increase in carbohydrate content by 45.81% and protein content by 123.68% in the cultivated tuber while fat content reduced by 13.04%. Cultivated tuber also showed an increase of up to 64.21% for total flavonoid-like compounds and 62.51% of total β-D-glucan compared to the wild tuber. The antioxidant activity of cultivated tuber and wild tuber was 760 and 840 µg mL-1, respectively. The cytotoxic activity of boiled water extract of cultivated tuber against a human lung cancer cell line (A549) was 65.50 ± 2.12 µg mL-1 and against a human breast cancer cell line (MCF7) was 19.35 ± 0.11 µg mL-1. β-D-glucan extract from the purification of boiled water extract of cultivated tuber showed cytotoxic activity at 57.78 ± 2.29 µg mL-1 against A549 and 33.50 ± 1.41 µg mL-1 against MCF7. However, the β-glucan extract from wild tuber did not show a cytotoxic effect against either the A549 or MCF7 cell lines. Also, neither of the extracts from cultivated tuber and wild tuber showed an effect against a normal cell line (MRC5). Compound profiling through by liquid chromatography mass spectrometry (LC/MS) showed the appearance of new compounds in the cultivated tuber. In conclusion, our cultivated tuber of tiger's milk mushroom using a new recipe cultivation technique showed improved nutrient and bioactive compound contents, and antioxidant and cytotoxic activities compared to the wild tuber. Further investigations are required to obtain a better quality of cultivated tuber.

Matched MeSH terms: MCF-7 Cells/drug effects
Fulltext Aporphine alkaloids from the leaves of Phoebe grandis (Nees) Mer. (Lauraceae) and their cytotoxic and antibacterial activities

Omar H, Hashim NM, Zajmi A, Nordin N, Abdelwahab SI, Azizan AH, et al.

Molecules, 2013 Jul 29;18(8):8994-9009.
PMID: 23899833 DOI: 10.3390/molecules18088994

The oxoaporphine alkaloid lysicamine (1), and three proaporphine alkaloids, litsericinone (2), 8,9,11,12-tetrahydromecambrine (3) and hexahydromecambrine A (4) were isolated from the leaves of Phoebe grandis (Nees) Merr. (Lauraceae). Compounds 2 and 3 were first time isolated as new naturally occurring compounds from plants. The NMR data for the compounds 2-4 have never been reported so far. Compounds 1 and 2 showed significant cytotoxic activity against a MCF7 (human estrogen receptor (ER+) positive breast cancer) cell line with IC₅₀ values of 26 and 60 µg/mL, respectively. Furthermore, in vitro cytotoxic activity against HepG2 (human liver cancer) cell line was evaluated for compounds 1-4 with IC₅₀ values of 27, 14, 81 and 20 µg/mL, respectively. Lysicamine (1) displayed strong antibacterial activity against Bacillus subtilis (B145), Staphylococcus aureus (S1434) and Staphylococus epidermidis (a clinically isolated strain) with inhibition zones of 15.50 ± 0.57, 13.33 ± 0.57 and 12.00 ± 0.00 mm, respectively. However, none of the tested pathogenic bacteria were susceptible towards compounds 2 and 3.

Matched MeSH terms: MCF-7 Cells/drug effects
Fulltext A Quantum Chemical and Statistical Study of Cytotoxic Activity of Compounds Isolated from Curcuma zedoaria

Hamdi OA, Anouar el H, Shilpi JA, Trabolsy ZB, Zain SB, Zakaria NS, et al.

Int J Mol Sci, 2015 Apr 27;16(5):9450-68.
PMID: 25923077 DOI: 10.3390/ijms16059450

A series of 21 compounds isolated from Curcuma zedoaria was subjected to cytotoxicity test against MCF7; Ca Ski; PC3 and HT-29 cancer cell lines; and a normal HUVEC cell line. To rationalize the structure-activity relationships of the isolated compounds; a set of electronic; steric and hydrophobic descriptors were calculated using density functional theory (DFT) method. Statistical analyses were carried out using simple and multiple linear regressions (SLR; MLR); principal component analysis (PCA); and hierarchical cluster analysis (HCA). SLR analyses showed that the cytotoxicity of the isolated compounds against a given cell line depend on certain descriptors; and the corresponding correlation coefficients (R2) vary from 0%-55%. MLR results revealed that the best models can be achieved with a limited number of specific descriptors applicable for compounds having a similar basic skeleton. Based on PCA; HCA and MLR analyses; active compounds were classified into subgroups; which was in agreement with the cell based cytotoxicity assay.

Matched MeSH terms: MCF-7 Cells/drug effects
Cimigenoside functions as a novel γ-secretase inhibitor and inhibits the proliferation or metastasis of human breast cancer cells by γ-secretase/Notch axis

Jia H, Liu M, Wang X, Jiang Q, Wang S, Santhanam RK, et al.

Pharmacol Res, 2021 Jul;169:105686.
PMID: 34022397 DOI: 10.1016/j.phrs.2021.105686

Breast cancer (BC) occurrence and development tremendously affect female health. Currently breast cancer targeted drugs are still scarce. Natural products have become the main source of targeted drug for breast cancer due to low toxicity and high efficiency. Cimigenoside, natural compound isolated and purified from Cimicifuga dahurica (Turcz.) Maxim has been suggested to utilize for breast cancer treatment, however the mechanism of action has not been elucidated yet. In this article, the antitumor potential of Cimigenoside against breast cancer in vitro and in vivo study. Moreover, we further predicted the possible binding mode of Cimigenoside with γ-secretase through molecular docking studies. The results show that Cimigenoside has a significant inhibitory effect towards the proliferation or metastasis of breast cancer cells via suppressing the Notch signaling pathway-mediated mitochondrial apoptosis and EMT (epithelial mesenchymal transition). In terms of mechanism, Cimigenoside could inhibit the activation of PSEN-1, the catalytic subunit of γ-secretase, and also by cleaving the Notch protein mediated by PSEN-1. Overall, our findings provide scientific support to utilize Cimigenoside as an effective targeted drug for clinical treatment of BC.

Matched MeSH terms: MCF-7 Cells/drug effects