Synthesis of NIR-II Absorbing Gelatin Stabilized Gold Nanorods and Its Photothermal Therapy Application against Fibroblast Histiocytoma Cells

The excellent photothermal properties of gold nanorods (Au-NRs) make them one of the most researched plasmonic photothermal nanomaterials. However, their biological applications have been hampered greatly due to surfactant-induced cytotoxicity. We herein report a simple synthesis of highly biocompatible gelatin stabilized Au-NRs (gelatin@Au-NRs) to address this issue. The optical and structural properties of the as-synthesized gelatin@Au-NRs were investigated by Zetasizer, Ultraviolet-Visible-Near Infrared (UV-Vis-NIR) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), and Fourier transform infrared spectroscopy (FTIR). The as-synthesized gelatin@Au-NRs were highly crystalline and rod-like in shape with an average length and diameter of 66.2 ± 2.3 nm and 10 ± 1.6 nm, respectively. The as-synthesized gelatin@Au-NRs showed high stability in common biological media (phosphate buffer saline and Dulbecco’s Modified Eagle’s Medium) compared to CTAB capped Au-NRs. Similarly, the gelatin@Au-NRs showed an improved heat production and outstanding cell viability against two different cancer cell lines; KM-Luc/GFP (mouse fibroblast histiocytoma cell line) and FM3A-Luc (breast carcinoma cell line) compared to CTAB capped Au-NRs and PEG@Au-NRs. An in vitro photothermal therapy study against KM-Luc/GFP showed that gelatin@Au-NRs effectively destroys the cancer cells.

Production, characterization and cytotoxicity effects of silver nanoparticles from Cystseira myrica

Background A green, eco-friendly approach to biosynthesizing silver nanoparticles has been reported for marine macroalga Cystseira myrica extract as a reducing agent. Methods Algal extract was prepared from the marine brown seaweed Cystoseira myrica. Different pH and temperature impact the green synthesis of silver nanoparticles suggesting that the synthesis depends greatly on pH and temperature. Silver nanoparticles have been detected by modifying the color of the algal extract and verified by the use of UV-vis and other characterizations. The Structure and characters of synthesized nanoparticles were confirmed using TEM, DLS, XRD, and FTIR. Cytotoxicity of the biosynthesized nanoparticles using provided cell lines of breast carcinoma cells (MCF-7) and human hepatocellular carcinoma cells (HepG2). Results Shape of silver nanoparticles at pH 9, 75°C for 30 min and was found to be suitable for the biosynthesis process and the AgNPs exhibited a characteristic absorption peak at 434nm. High resolution Electron Microscope Transmission (HR-TEM) reported polydisperse and spherical shapes ranging from 8 to 15 nm. High attractive and repulsive forces between each nanoparticle were recorded with an average zeta potential value of approximately −29.3 mV for C. myrica extract NPs. The X-ray diffraction study revealed the crystalline structure of silver nanoparticles. FT-IR has shown the bioreduction of silver ions to silver nanoparticles through biomolecules found in C. myrica extract. Silver nanoparticles have been found to have anticancer activity. The cytotoxicity assay was studied against MCF-7 and HepG2 at various concentrations (100, 50, 25, 12.5, 6.25, 3.125, 1.56, 0.78, 0.39, 0.2 and 0.1 μg/mL). By increasing the concentration of AgNPs from 0.1 to 100 μg/mL the maximum percentage of viability against MCF-7 and HepG2 cell line decreased from 94.55 ± 7.55 to 19.879 ± 0.503 and from 78.56 ± 11.36 to 25.81 ± 2.66 after time exposure respectively. Conclusions The silver nanoparticles from Cystoseira myrica have cytotoxicity activity against MCF-7 breast carcinoma cell line and HepG2 human hepato cellular carcinoma cell line.

Design, Synthesis and Evaluation of Core Scaffold Pyrazolone Fused Thiazolidinone Derivatives as Anticancer Agents

Background: Cancer is the world's second leading cause of death, accounting for an estimate of more than 10 million deaths annually. The most common type of cancers in women are breast, endometrial, cervical, ovarian, colorectal, lung, and skin cancers.Among these, breast cancer is the most common in women of all ages. Human epidermal growth factor receptor 2 breast cancer is widely seen in women which test positive for the protein HER2. This protein is present in one-fifth of every breast cancer cell, which promotes the growth of cancer cells. There are several compounds available for the treatment of HER2 breast cancer in the market with varying promise in their efficacy and safety on HER2 treatment. Objective: To design synthesis and evaluation of core scaffold pyrazolone fused thiazolidinone derivatives as anticancer agents. Methods: In this study, the core scaffold pyrazolone fused thiazolidinone derivatives were designed, synthesized, and analyzed for the anticancer activity using breast carcinoma cell line (MCF-7), against the standard drug Doxorubicin. Results: Many thiazoles, fused thiazole, and pyrazole derivatives have been found to have anti-cancer and other properties. In this study, the compound 1-phenyl-3-methyl-5-pyrazolones was allowed to react with diverse benzoyl chloride as well as primary amine derivatives and transformed into ’A series of Pyrazolone fused Thiazolidinone derivatives 4A1-4A10 and 4B1- 4B10. Computational studies by Schrodinger Glide XP using the Protein 3RCD which act on the human epidermal growth factor receptor’’ was performed on the selected scheme initially and further from the docked score data the synthesis of pyrazolone fused thiazolidinone was performed. Conclusion: Among the compounds synthesized, five compounds (4A6 − 3.4 kcal/mol, 4B4 − 3.0 kcal/mol, 4A3 − 2.2 kcal/mol, 4B2 − 1.6 kcal/mol, and 4A9 − 1.3 kcal/mol) shown promising binding affinities against epidermal growth factor receptor kinase. The cytotoxic potential of the compounds was examined using a breast carcinoma cell line (MCF-7), which shown cytotoxicity close to Doxorubicin (standard drug). Our findings are an important step forward in the development of novel anticancer agents.

CHEMICAL AND BIOLOGICAL ANALYSIS OF THE BIOCTIVE FRACTIONS OF THE LEAVES OF SCAEVOLA TACCADA (GAERTN.) ROXB

Objective: Scaevola taccada. (Gaertn.) Roxb. is widely dispersed all along the coasts of Africa. It is used in folk medicine for diversity of ailments. This study aims to investigate the major phytoconstituents and biological activities of the leaves of S. taccada (Gaertn.) Roxb. Methods: In vitro biological examination viz. antimicrobial, cytotoxic and antioxidant activities of the ethanol extract of the leaves (EE) and its fractions; (petroleum ether (PE), methylene chloride (MC), ethyl acetate (EA) and n-butanol(BuOH)) were carried out. Estimation of the phytochemicals of biologically active fractions was done. Results: n-butanol fraction displayed remarkable antimycobacterium activity. Petroleum ether as well as n-butanol fractions evidenced a cytotoxic effect on breast carcinoma cell line (MCF7) and colon carcinoma cell line (HCT) with IC50 11.7 and 15.04 µg/ml respectively. Moreover, ethyl acetate fraction exhibits an antioxidant effect with EC50 476.7±0.57 µg/ml. n-tetradecane 1, α-amyrin palmitate 2, α-amyrin acetate 3, α-amyrin 4, stigmasterol 5, luteolin-7-O-β-glucoside 6, rutin 7 and alidyjosioside 8 were identified in S. taccada (Gaertn.) Roxb. leaves. Conclusion: Petroleum ether fraction is a cytotoxic candidate, especially against (MCF-7). It exhibited a moderate antifungal and antibacterial against certain Gram-positive bacteria. Ethyl acetate showed an antioxidant effect along with moderate antifungal activity. n-butanol fraction exerted potential antimycobacterial, significant cytotoxic activity against (HCT), good antifungal and antibacterial against Gram-positive and Gram-negative bacteria. Stigmasterol, luteolin-7-O-β-glucoside, rutin and alidyjosioside were isolated for the first time from S. taccada (Gaertn.) Roxb. Leaves.

Two New Geranylated Biphenyl Esters From Artocarpus altilis

Two new geranylated biphenyl esters, 2,3′,4,4′-tetrahydroxy-3-geranyl-5-carboxyethyl-biphenyl methyl ester (1), 2,3′,4,4′-tetrahydroxy-3-geranyl-5-carboxymethyl-biphenyl methyl ester (2), together with 4 known compounds were isolated from the methanol extract of the leaves of Artocarpus altilis. Their structures were established by spectroscopic means and by comparison with literature data. Compound 1 possessed moderate cytotoxicity toward MDA-MB-231 (a breast carcinoma cell line) with a half-maximal inhibitory concentration value of 30 µM and inhibited the growth of 8 bacteria, including gram-negative and gram-positive organisms, but was inactive against fungi.

The Effect of Bitter Melon (Momordica charantia) Extract on the Uptake of 99mTc Labeled Paclitaxel: In Vitro Monitoring in Breast Cancer Cells

Background: Bitter Melon Extract (BME) is widely used for the treatment of various diseases worldwide due to its rich phytochemical and antioxidant content. The well-known anti-cancer drug Paclitaxel (PAC) plays a major role in the treatment of various cancer types such as ovarian, breast, and lung cancer. Technetium-99m (99mTc) radiolabeled paclitaxel is emerging as an imaging probe for breast cancer in vivo. 99mTc labeled compounds have been attracting more scientific attention since the achievement of earlier researches in Nuclear Medicine. People consume several types of diets of plant origin without knowing the interaction with radiolabeled compounds or radiopharmaceuticals. Objectives: In the current study, we aimed to monitor the potential effects of the BME on the uptake of 99mTc labeled Paclitaxel (99mTc-PAC) against MCF-7 (ER+) and MDA-MB-231 (ER-) cell lines by using in vitro methods. Methods: BME was obtained by the extraction of BM seeds by 80% ethanol. PAC was labeled with 99mTc by stannous chloride (SnCl2) as a reducing agent. Cytotoxicity and incorporation assays were performed on MCF-7 and MDA-MB-231 cells within the cell culture studies. Results: The uptake value of 99mTc-PAC on MCF-7 cells at 240 minutes was 6.20% and BME treated 99mTc- PAC value was 17.39%. Conclusion: It is observed that BME treatment has a significant effect on the uptake of 99mTc-PAC on MCF-7 cells which is a known estrogen receptor-positive breast carcinoma cell line. It is concluded that this effect could be due to the estrogen receptor-dependent interaction of BME.

Radioiodinated Ginger Compounds (6-gingerol and 6-shogaol) and Incorporation Assays on Breast Cancer Cells

Background: 6-Gingerol (6G) and 6-Shogaol (6S) are the main active components of ginger. 6-Gingerol is known for its anti-metastatic and anti-invasive pharmacological activities on cancer cells, besides, 6-Shogaol also inhibits breast cancer cell invasion. Objective: In this study, radioiodination (131I) of 6G and 6S was aimed. Additionally, it is aimed to monitor their incorporation behavior on breast cancer cell lines. Methods: 6-Gingerol was isolated from the fresh ginger-roots extract, additionally, dehydrated to obtain 6-Shogaol. 6G and 6S were radioiodinated using iodogen method. Quality control studies of radioiodinated ginger compounds (6G and 6S) were performed by thin layer radio-chromatography. In vitro studies of radioiodinated ginger compounds on MCF-7 and MDA-MB-231 cells were performed with incorporation assays. Results: 6-Gingerol and 6-Shogaol were radioiodinated (131I-6G and 131I-6S) in high yields over 95%. 131I-6S demonstrated higher incorporation values than 131I-6G on MDA-MB-231 cells. Incorporation behavior of 131I-6G and 131I-6S was similar to MCF-7 cells. Conclusion: It has been observed that ginger compounds were radioiodinated successfully and 131I-6S have a noteworthy incorporation on MDA-MB-231 cells which is a known breast carcinoma cell line with highly invasive characteristics.

Novel Anticancer NHC*-Gold(I) Complexes Inspired by Lepidiline A

N-Heterocyclic carbene gold(I) complexes derived from 1,3-dibenzyl-4,5-diphenylimidazol-2-ylidene (NHC*) represent a promising class of anticancer drugs. Complexes of the type NHC*-Au-L (L = Br−, I−, C≡C-R) and [NHC*-Au-L]+ (L = NHC*, PPh3) have been synthesised. The X-ray crystal structures of all gold(I) complexes are presented; aurophilic interactions were observed in five of the complexes. The anticancer activity was assessed via MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)-based proliferation assays against the human colon carcinoma cell line HCT-116wt and the multidrug-resistant human breast carcinoma cell line MCF-7topo. Most complexes showed good cytotoxicity with IC50 values in the low micromolar range, while excellent sub-micromolar activity was observed for 2c, 3a and 3b. Generally, the activity of the ligands studied was as follows: carbene > phosphine > alkyne > halide, with an exception for the highly active iodido derivative 2c.

Nucleosomes effectively shield DNA from radiation damage in living cells

Eukaryotic DNA is organized in nucleosomes, which package DNA and regulate its accessibility to transcription, replication, recombination and repair. Here, we show that in living cells nucleosomes protect DNA from high-energy radiation and reactive oxygen species. We combined sequence-based methods (ATAC-seq and BLISS) to determine the position of both nucleosomes and double strand breaks (DSBs) in the genome of nucleosome-rich malignant mesothelioma cells, and of the same cells partially depleted of nucleosomes. The results were replicated in the human MCF-7 breast carcinoma cell line. We found that, for each genomic sequence, the probability of DSB formation is directly proportional to the fraction of time it is nucleosome-free; DSBs accumulate distal from the nucleosome dyad axis. Nucleosome free regions and promoters of actively transcribed genes are more sensitive to DSB formation, and consequently to mutation. We argue that this may be true for a variety of chemical and physical DNA damaging agents.