Cytotoxic Potential from the Extracellular Filtrate from Aspergillus niveus Cultured in YPD Medium against Human Tumor Cells

Different fungal species, especially from the genus Aspergillus, have been reported as producers of small molecules, including proteins, with biological activity and a better understanding of their sources, structure, function and toxicity is essential for their biotechnological applications. According to this, our aim was to evaluate the cytotoxic activity of the extracellular filtrate produced by A. niveus. The crude filtrate obtained in YPD medium containing 18 kDa protein, after cultivation for 120 h, was selected for cytotoxic assay, assessed by Giemsa staining, against different human tumor cell lines. Crude filtrate inhibited (from 27% to 50%) the ONS-76 (medulloblastoma), HT144T (melanoma), HOS (osteosarcoma), T98G (glioblastoma) human tumor cell lines and MRC-5 (fibroblasts) human normal cells, at 20 µg/mL for 72 h treatment. According to this, the 18 kDa protein band and the fractions obtained after DEAE-Cellulose procedure were evaluated through mass spectrometry (MS/MS) analysis, revealing the presence of peptides with similarity to the alpha-sarcin, mitogillin and Aspf1 ribotoxins described for other Aspergillus species. In conclusion, the A. niveus extracellular filtrate containing ribotoxin-like proteins reduced, in vitro, the growth of human tumor cell lines indicating their biotechnological potential, indicating a possible future application in the elaboration of immunotoxins.

Download Full-text

Synthesis and Cytotoxicity of New Mannich Bases of 6-[3-(3,4,5-Trimetoxyphenyl)-2- propenoyl]-2(3H)-Benzoxazolone

Letters in Drug Design & Discovery ◽

10.2174/1570180816666190730164952 ◽

2020 ◽

Vol 17 (4) ◽

pp. 512-517

Author(s):

Ognyan Ivanov Petrov ◽

Yordanka Borisova Ivanova ◽

Mariana Stefanova Gerova ◽

Georgi Tsvetanov Momekov

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Biological Activities ◽

Human Tumor ◽

Mannich Bases ◽

In Vitro Cytotoxicity ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

Background: Chemotherapy is one of the mainstays of cancer treatment, despite the serious side effects of the clinically available anticancer drugs. In recent years increasing attention has been directed towards novel agents with improved efficacy and selectivity. Compounds with chalcone backbone have been reported to possess various biological activities such as anticancer, antimicrobial, anti-inflammatory, analgesic, antioxidant, etc. It was reported that aminomethylation of hydroxy chalcones to the corresponding Mannich bases increased their cytotoxicity. In this context, our interest has been focused on the design and synthesis of the so-called multi-target molecules, containing two or more pharmacophore fragments. Methods: A series of Mannich bases were synthesized by the reaction between 6-[3-(3,4,5- trimethoxyphenyl)-2-propenoyl]-2(3Н)-benzoxazolone, formaldehyde, and a secondary amine. The structures of the compounds were confirmed by elemental analysis, IR and NMR spectra. The new Mannich bases were evaluated for their in vitro cytotoxicity against a panel of human tumor cell lines, including BV-173, SKW-3, K-562, HL-60, HD-MY-Z and MDA-MB-231. The effects of selected compounds on the cellular levels of glutathione (GSH) were determined. Results: The new compounds 4a-e exhibited concentration-dependent cytotoxic effects at micromolar concentrations in MTT-dye reduction assay against a panel of human tumor cell lines, similar to those of starting chalcone 3. The tested agents led to concentration - dependent depletion of cellular GSH levels, whereby the effects of the chalcone prototype 3 and its Mannich base-derivatives were comparable. Conclusion: The highest chemosensitivity to the tested compounds was observed in BV- 173followed by SKW-3 and HL-60 cell lines.

Download Full-text

Pharmacoinformatics and Preclinical Studies of NSC765690 and NSC765599, Potential STAT3/CDK2/4/6 Inhibitors with Antitumor Activities against NCI60 Human Tumor Cell Lines

Biomedicines ◽

10.3390/biomedicines9010092 ◽

2021 ◽

Vol 9 (1) ◽

pp. 92

Author(s):

Bashir Lawal ◽

Yen-Lin Liu ◽

Ntlotlang Mokgautsi ◽

Harshita Khedkar ◽

Maryam Rachmawati Sumitra ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Cancer Cell ◽

Human Tumor ◽

Cancer Cell Lines ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines ◽

Anti Cancer

Signal transducer and activator of transcription 3 (STAT3) is a transcriptional regulator of a number of biological processes including cell differentiation, proliferation, survival, and angiogenesis, while cyclin-dependent kinases (CDKs) are a critical regulator of cell cycle progression. These proteins appear to play central roles in angiogenesis and cell survival and are widely implicated in tumor progression. In this study, we used the well-characterized US National Cancer Institute 60 (NCI60) human tumor cell lines to screen the in vitro anti-cancer activities of our novel small molecule derivatives (NSC765690 and NSC765599) of salicylanilide. Furthermore, we used the DTP-COMPARE algorithm and in silico drug target prediction to identify the potential molecular targets, and finally, we used molecular docking to assess the interaction between the compounds and prominent potential targets. We found that NSC765690 and NSC765599 exhibited an anti-proliferative effect against the 60 panels of NCI human cancer cell lines, and dose-dependent cytotoxic preference for NSCLC, melanoma, renal, and breast cancer cell lines. Protein–ligand interactions studies revealed that NSC765690 and NSC765599 were favored ligands for STAT3/CDK2/4/6. Moreover, cyclization of the salicylanilide core scaffold of NSC765690 mediated its higher anti-cancer activities and had greater potential to interact with STAT3/CDK2/4/6 than did NSC765599 with an open-ring structure. NSC765690 and NSC765599 met the required safety and criteria of a good drug candidate, and are thus worthy of further in-vitro and in-vivo investigations in tumor-bearing mice to assess their full therapeutic efficacy.

Download Full-text

Synthesis and Characterization of New Palladium(II) Complexes with Ligands Derived from Furan-2-carbaldehyde and Benzaldehyde Thiosemicarbazone and their in vitro Cytotoxic Activities against Various Human Tumor Cell Lines

Zeitschrift für Naturforschung B ◽

10.1515/znb-2010-1015 ◽

2010 ◽

Vol 65 (10) ◽

pp. 1271-1278 ◽

Cited By ~ 4

Author(s):

Wilfredo Hernández ◽

Juan Paz ◽

Fernando Carrasco ◽

Abraham Vaisberg ◽

Jorge Manzur ◽

...

Keyword(s):

Tumor Cell ◽

Cell Lines ◽

Human Tumor ◽

Myelogenous Leukemia ◽

Cytotoxic Activities ◽

Spectroscopic Techniques ◽

Tumor Cell Lines ◽

Human Tumor Cell ◽

Human Tumor Cell Lines

With the ligands 4-phenyl-1-(furan-2-carbaldehyde)thiosemicarbazone, HTSC1, (1), 4-phenyl-1- (5´-phenyl-furan-2-carbaldehyde)thiosemicarbazone, HTSC2 (2), o-methoxy-benzaldehydethiosemicarbazone, HTSC3 (3), and o-cyano-benzaldehydethiosemicarbazone, HTSC4 (4), the corresponding palladium(II) complexes, Pd(TSC1)2 (5), Pd(TSC2)2 (6), Pd(TSC3)2 (7), and Pd(TSC4)2 (8) were synthesized and characterized by elemental analysis and spectroscopic techniques. The crystal structure of Pd(TSC3)2 (7) was determined by single-crystal X-ray diffraction. Complex 7 shows a squareplanar geometry, where two deprotonated ligands are coordinated to the PdII center through the nitrogen and sulfur atoms in a trans arrangement. In vitro antitumor studies against different human tumor cell lines have revealed that the palladium(II) complexes 5- 8 are more cytotoxic (IC50 values in the range of 0.21 - 3.79 μM) than their corresponding ligands (1 - 4) (> 60 μM). These results indicate that the antiproliferative activity is enhanced when thiosemicarbazone ligands are coordinated to the metal. Among the studied palladium(II) complexes, 8 exhibits high antitumor activity on K562 chronic myelogenous leukemia cells with a low value of the inhibitory concentration (IC50 = 0.21 μM).

Download Full-text