Anticancer and antibacterial secondary metabolites from the endophytic fungus Penicillium sp. CAM64 against multi-drug resistant Gram-negative bacteria.

Background: The emergence of multiple-drug resistance bacteria has become a major threat and thus calls for an urgent need to search for new effective and safe anti-bacterial agents. Objectives: This study aims to evaluate the anticancer and antibacterial activities of secondary metabolites from Penicillium sp. , an endophytic fungus associated with leaves of Garcinia nobilis . Methods: The culture filtrate from the fermentation of Penicillium sp. was extracted and analyzed by liquid chromatography– mass spectrometry, and the major metabolites were isolated and identified by spectroscopic analyses and by comparison with published data. The antibacterial activity of the compounds was assessed by broth microdilution method while the anticancer activity was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Results: The fractionation of the crude extract afforded penialidin A-C (1-3), citromycetin (4), p-hydroxyphenylglyoxalaldoxime (5) and brefelfin A (6). All of the compounds tested here showed antibacterial activity (MIC = 0.50 – 128 μg/mL) against Gramnegative multi-drug resistance bacteria, Vibrio cholerae (causative agent of dreadful disease cholera) and Shigella flexneri (causative agent of shigellosis), as well as the significant anticancer activity (LC50 = 0.88 – 9.21 μg/mL) against HeLa cells. Conclusion: The results obtained indicate that compounds 1-6 showed good antibacterial and anticancer activities with no toxicity to human red blood cells and normal Vero cells.

Isolation of a potential anticancer agent with protein phosphatase inhibitory activity from soil-derived Penicillium sp strain H9318

Purpose: To determine the effect of the secondary metabolites from Penicillium sp. H9318 on cytotoxicity and cell cycle progression. Methods: A yeast PP1 inhibitory screening system was carried out to confirm the presence of anti- PP1c activity in crude acetone extracts of strain H9318. The extracts were fractionated and identified as Fraction S1 and Citrinin 9318 (CTN9318). Various cancer cell lines were used to test for the toxicity of the crude acetone extracts, Fraction S1 and Citrinin 9318, using MTT viability assay. Results: It was found that a colorectal cancer cell line, HT-29, was susceptible to Fraction S1 and Citrinin 9318. A propidium iodide (PI)-incorporated DNA assay was used to show that there was G2/M arrest in HT-29 by Citrinin 9318. Conclusion: Citrinin 9318 inhibits the viability of HT-29 via mitotic block. The results suggest that Citrinin 9318 is capable of exerting cytotoxicity and mitotic arrest in a colon cancer cell line, HT29

Cytotoxic, anti-inflammatory and antioxidant activities of four different extracts of Galega officinalis L (Goat’s rue)

Purpose: To evaluate the cytotoxic, anti-inflammatory and antioxidant activities of four different solvent extracts obtained from the aerial parts of Galega officinalis L Methods: The hexane, DCM, methanol and water extracts of G. officinalis were successively obtained by soxhlet extraction method. The cytotoxic activity of the extracts was assessed against human lung carcinoma (A-549), human colorectal adenocarcinoma (HT-29), human brain glioblastoma (U-87), and colon adenocarcinoma (DLD-1) by Resazurine test. The antioxidant activity of extracts were determined by Folin-Ciocalteau, oxygen radical absorbing capacity (ORAC), and 2’.7’-dichlorofluorescin-diacetate (DCFH-DA) cell-based assay while their anti-inflammatory activity was determined by nitric oxide (NO) assay. Results: DCM extract showed strong cytotoxic activity against lung adenocarcinoma and brain glioblastoma cell lines, with IC50 (concentration inhibiting 50 % of cell growth) values of 11 ± 0.4 and 16 ± 3 μg/mL, respectively. The hexane extract showed moderate anticancer activity against the same cell lines (59 ± 13 and 63 ± 16 μg/mL, respectively). DCM extract also showed significant anti-inflammatory activity, inhibiting NO release by 86.7 % at 40 μg/mL in lipopolysaccharide (LPS) - stimulated murine RAW 264.7 macrophages. Of all test extracts, the methanol extract of G. officinalis showed the highest antioxidant activity with 2.33 ± 0.09 μmol Trolox/mg , 7.10 ± 0.9 g tannic acid equivalent (TAE), and IC50 of 44 ± 4 μg/mL. Conclusion: The findings of this study suggest that DCM extract may possess anticancer effect against lung adenocarcinoma and brain glioblastoma, as well as serve as an anti-inflammatory agent.

Characterization of volatile compounds of Albertisia papuana Becc root extracts and cytotoxic activity in breast cancer cell line T47D

Purpose: To evaluate the cytotoxic activity of chloroform and water root extracts of Albertisia papuana Becc. on T47D cell line and identify the volatile compounds of the extracts. Methods: The plant roots were extracted with chloroform and water using maceration and boiling methods, respectively. The cytotoxicity of the extracts on T47D were determined using 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Doxorubicin was used as reference drug in the cytotoxicity test while Probit analysis was used to calculate the Median Growth Inhibitory Concentration IC50 of the extracts. The volatile compounds in the chloroform and water root extracts were analyzed using Gas Chromatography-Mass Spectrophotometry GC-MS. Results: The IC50 of the chloroform and water extracts were 28.0 ± 6.0 and 88.0 ± 5.5 μg/mL, respectively whereas that of doxorubicin was 8.5 ± 0.1 μg/mL. GC-MS results showed that there were 46 compounds in the chloroform extract, out of which the five major components are ethyl linoleate (49.68 %), bicyclo (3.3.1) non-2-ene (29.29 %), ethyl palmitate (5.06 %), palmitic acid (3.67 %) and ethyl heptadecanoate (1.57 %).The water extract consisted of three compounds, butanoic acid (15.58 %); methyl cycloheptane (3.45 %), and methyl 2-O-methylpentofuranoside (80.96 %). Conclusion: The chloroform root extract of A. papuana Becc. had a fairly potent anticancer activity against breast cancer cells and may be further developed as an anticancer agent. Its major components were fatty acids and fatty acid esters.

Anti-cancer and antioxidant properties of phenolics isolated from Toona sinensis A Juss acetone leaf extract

Purpose: To investigate the antioxidant and anticancer activities of phenolics from the leaf extract of Toona sinensis (TS). Methods: Acetone leaf extract of TS was screened for total phenolic and flavanoid contents, and the flanonoids were subjected to high performance liquid chromatographic (HPLC) analysis. Antioxidant properties were assessed via oxygen radical absorbance capacity (ORAC), peroxyl radical scavenging capacity (PSC) and cellular antioxidant activity (CAA), while anti-proliferative activity ins HepG2 cell line was assessed using methylene blue assay. Results: The extract contained 36.02 ± 0.24 mg of gallic acid equiv/g dry weight (DW) and 20.24 ± 1.73 mg of catechin equiv/g DW of total phenolic and total flavonoid, respectively. The levels of rutin and quercitrin were 0.51 and 19.55 mg/g, respectively. Epicatechin, gallic acid, quercitin, isoquercetin were not detected. The extract showed significant antioxidant potential and high anti-proliferation capacity with low cytotoxicity against HepG2 cell in vitro. The underlying mechanism of anti-proliferative effect was induction of apoptosis. Conclusion: TS leaf extract possesses significant in vitro antioxidant properties and anti-proliferative effect against HepG2 cells, which make it a potential anticancer drug source.

Design, synthesis and antiproliferative activity of hydroxyacetamide derivatives against HeLa cervical carcinoma cell and breast cancer cell line

Purpose: To design and develop a new series of histone deacetylase inhibitors (FP1 - FP12) and evaluate their inhibitory activity against hydroxyacetamide (HDAC) enzyme mixture-derived HeLa cervical carcinoma cell and MCF-7. Methods: The designed molecules (FP1 - FP12) were docked using AUTODOCK 1.4.6. FP3 and FP8 showed higher interaction comparable to the prototypical HDACI. The designed series of 2-[[(3- Phenyl/substituted Phenyl-[4-{(4-(substituted phenyl)ethylidine-2-Phenyl-1,3-Imidazol-5-One}](-4H- 1,2,4-triazol-5-yl)sulfanyl]-N-hydroxyacetamide derivatives (FP1-FP12) was synthesized by merging 2- [(4-amino-3-phenyl-4H- 1, 2, 4-triazol-5-yl) sulfanyl]-N-hydroxyacetamide and 2-{[4-amino-3-(2- hydroxyphenyl)-4H-1,2, 4-triazol-5-yl]sulfanyl}-N hydroxyacetamide derivatives with aromatic substituted oxazolone. The biological activity of the synthesized molecule (FP1-FP12) was evaluated against HDAC enzyme mixture-derived HeLa cervical carcinoma cell and breast cancer cell line (MCF-7). Results: HDAC inhibitory activity of FP10 showed higher IC50 (half-maximal concentration inhibitory activity) of 0.09 μM, whereas standard SAHA molecule showed IC50 of 0.057 μM. On the other hand, FP9 exhibited higher GI50 (50 % of maximal concentration that inhibited cell proliferation) of 22.8 μM against MCF-7 cell line, compared with the standard, adriamycin, with GI50 of (-) 50.2 μM. Conclusion: Synthesis, spectral characterization, and evaluation of HDAC inhibition activity and in vitro anticancer evaluation of novel hydroxyacetamide derivatives against MCF-7 cell line have been achieved. The findings indicate the emergence of potentialanticancer compounds.