Machine Learning Assisted Classification of Cell Lines and Cell States on Quantitative Phase Images

In this report, we present implementation and validation of machine-learning classifiers for distinguishing between cell types (HeLa, A549, 3T3 cell lines) and states (live, necrosis, apoptosis) based on the analysis of optical parameters derived from cell phase images. Validation of the developed classifier shows the accuracy for distinguishing between the three cell types of about 93% and between different cell states of the same cell line of about 89%. In the field test of the developed algorithm, we demonstrate successful evaluation of the temporal dynamics of relative amounts of live, apoptotic and necrotic cells after photodynamic treatment at different doses.

Evaluation and Optimization of Poly-D-Lysine as a Non-Natural Cationic Polypeptide for Gene Transfer in Neuroblastoma Cells

Cationic polypeptides and cationic polymers have cell-penetrating capacities and have been used in gene transfer studies. In this study, we investigate the capability of a polymer of D-lysine (PDL), a chiral form of α-Poly-lysine, as a possible nonviral vector for releasing genetic materials to neuroblastoma cells and evaluate its stability against proteases. We tested and compared its transfection effectiveness in vitro as a vehicle for the EGFP plasmid DNA (pDNA) reporter in the SH-SY5Y human neuroblastoma, HeLa, and 3T3 cell lines. Using fluorescent microscopy and flow cytometry, we demonstrated high transfection efficiencies based on EGFP fluorescence in SH-SY5Y cells, compared with HeLa and 3T3. Our results reveal PDL as an efficient vector for gene delivery specifically in the SH-SY5Y cell line and suggest that PDL can be used as a synthetic cell-penetrating polypeptide for gene therapy in neuroblastoma cells.

Evaluation of new sulfathiazole derivatives as antiproliferative agents

Objectives Sulfonamide group is an important scaffold used for generating new building blocks with diverse biological activities. Considering priority of the sulfonamide structure, seven new sulfathiazole derivatives were synthesized and evaluated for their antiproliferative activity, in this study. Materials and methods Compounds 2a–g were synthesized using a two-step synthetic procedure starting from commercially available sulfathiazole. The antiproliferative activity of the compounds was investigated against A549 and NIH/3T3 cell lines by MTT assay, matrix metalloproteinase-9 (MMP-9) and cathepsin inhibition tests. Results Compound 2b bearing triazole ring exhibited highest inhibitory activity (IC50: 12.33 μg/mL) with selective profile which was better than cisplatin and it also inhibited MMP-9 with 53.67% percentage. Compounds 2c and 2e inhibited cathepsin L with percentages of 62.75 and 57.25%, whereas cathepsin D was poorly inhibited by the compounds. Conclusions Target compounds exhibited high to moderate antiproliferative activity and they displayed higher MMP-9 inhibition than cathepsin inhibition activity. 2b and 2e were identified as the most active compounds when evaluated, biologically.

Characterization of isolated compounds from Morus spp. and their biological activity as anticancer molecules

Introduction: The genus Morus is well known for its medicinal benefits from time immemorial. The present work reported the health-promoting properties of the biologically active molecules present in different species of the genus Morus. Methods: Different solvent extracts of the three plant species of Morus were investigated initially for their antioxidant effects, followed by in vitro anticancer studies against MCF7 and 3T3 cell lines along with their bioactive isolates viz. cathafuran-B, moracin-M, and Ursolic acid. Further, in silico docking studies were performed for the isolated compounds to predict their probable mode of interaction with P38Map Kinase. Results: The results indicated that all three species under study possessed remarkable antioxidant effects which are supported by a linear and positive correlation between different antioxidant activities. The in vitro cell antiproliferative test indicated that the cell survivability decreased with an increase in the concentration of extracts and compounds. Among the extracts, M. laevigata methanol extract showed 21.57, 6.27% of cell survival against MCF7 and 3T3 cell lines at 800 µg/mL concentration while among the isolated compounds, ursolic acid showed 8.46, 17.58% of cell survival at 200 µg/mL concentration. Among the three compounds docked, ursolic acid showed greater binding affinity towards the target protein in terms of its binding energy (-9.97 kJ/mol) compared to Cathafuran B (-8.35 kJ/mol) and Moracin M (-6.91 kJ/mol). Conclusion: The study generated interesting results in terms of health benefits of Morus species by documenting their antioxidant and anticancer activities, thereby validating the folk claims of therapeutic benefits of mulberry.

New Series of Double-Modified Colchicine Derivatives: Synthesis, Cytotoxic Effect and Molecular Docking

Colchicine is a well-known anticancer compound showing antimitotic effect on cells. Its high cytotoxic activity against different cancer cell lines has been demonstrated many times. In this paper we report the syntheses and spectroscopic analyses of novel colchicine derivatives obtained by structural modifications at C7 (carbon-nitrogen single bond) and C10 (methylamino group) positions. All the obtained compounds have been tested in vitro to determine their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX, and BALB/3T3 cell lines. The majority of obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin and cisplatin against the tested cancerous cell lines. Additionally, most of the presented derivatives were able to overcome the resistance of LoVo/DX cells. Additionally, their mode of binding to β-tubulin was evaluated in silico. Molecular docking studies showed that apart from the initial amides 1 and 2, compound 14, which had the best antiproliferative activity (IC50 = 0.1–1.6 nM), stood out also in terms of its predicted binding energy and probably binds best into the active site of βI-tubulin isotype.

Synthesis, Antiproliferative Activity and Molecular Docking Studies of Novel Doubly Modified Colchicine Amides and Sulfonamides as Anticancer Agents

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

Influence of amide versus ester linkages on the anticancer properties of the new flavone–biotin conjugates

Novel biotinylated C-6 substituted flavones were synthesised by a one-step method that connects biotin to 6-hydroxyflavone and 6-aminoflavone by esterification and amidation of hydroxyl and amino groups, respectively. The obtained compounds, 6-O-biotinylflavone and 6-biotinylamidoflavone, are the bifunctional molecules composed of a flavone moiety as a fluorescent reporter and biotin as a cancer-targeting unit. Antiproliferative activity was evaluated using SRB assays in MCF-7, MCF-10A, HepG2, MDA-MB-231, 4T1, and Balb/3T3 cell lines. In vitro evaluation revealed that compounds with biotin moiety displayed better cell selectivity between the cancer and normal cells than the parental substrates. These results indicate that anticancer effect is not related to the position of biotin moiety, but it is related to the presence of ester or amide bond. 6-O-Biotinylflavone was more active than 6-hydroxyflavone against human breast (MDA-MB-231) and liver (HepG2) cancer cells with IC50 (concentration of tested agent that inhibits proliferation of the cell population by 50%) values equal to 78.5 ± 18.8 μM and 133.2 ± 14.2 μM, respectively. Non biotinylated 6-aminoflavone was more active than 6-biotinylamidoflavone against all tested cell lines, with IC50 values between 34.3 ± 9.1 μM (4T1) and 173.86 ± 24.3 μM (MCF-7).

The Bio-Safety Concerns of Three Domestic Temporary Hair Dye Molecules: Fuchsin Basic, Victoria Blue B and Basic Red 2

Hair-coloring products include permanent, semi-permanent and temporary dyes that vary by chemical formulation and are distinguished mainly by how long they last. Domestic temporary hair dyes, such as fuchsin basic, basic red 2 and Victoria blue B, are especially popular because of their cheapness and facile applications. Despite numerous studies on the relationship between permanent hair dyes and disease, there are few studies addressing whether these domestic temporary hair dyes are associated with an increased cancer risk. Herein, to ascertain the bio-safety of these temporary hair dyes, we comparatively studied their percutaneous absorption, hemolytic effect and cytotoxic effects in this paper. Furthermore, to better understand the risk of these dyes after penetrating the skin, experimental and theoretical studies were carried out examining the interactions between the dyes and serum albumins as well as calf thymus (CT)-DNA. The results showed that these domestic temporary hair dyes are cytotoxic with regard to human red blood cells and NIH/3T3 cell lines, due to intense interactions with bovine serum albumin (BSA)/DNA. We conclude that the temporary hair dyes may have risk to human health, and those who use them should be aware of their potential toxic effects.