Bimetallic bis-Aroyldihydrazone-Isatin Complexes of High O=V(IV) and Low Cu(II) Valent Ions as Effective Biological Reagents for Antimicrobial and Anticancer Assays.

Due to the versatile bioreactivity of aroyldihydrazone complexes as cost-effective alternatives with different transition metals, two novel bimetallic homo-complexes (VOLph and CuLph) were prepared via the coordination of a terephthalic dihydrazone diisatin ligand (H2Lph) with VO2+ and Cu2+ ions, respectively. The structure elucidation was confirmed by alternative spectral methods. Biologically, the H2Lph ligand and its MLph complexes (M2+ = VO2+ or Cu2+) were investigated as antimicrobial and anticancer agents. Their biochemical activities towards ctDNA (calf thymus DNA) were estimated using measurable titration viscometrically and spectrophotometrically, as well as the gel electrophoresis technique. The growth inhibition of both VOLph and CuLph complexes against microbial and cancer cells was measured, and the inhibition action, MIC, and IC50 were compared to the inhibition action of the free H2Lph ligand. Both VOLph and CuLph showed remarkable interactive binding with ctDNA compared to the free ligand H2Lph, based on Kb = 16.31, 16.04 and 12.41 × 107 mol-1 dm3 and ΔGb≠ = 47.11, -46.89, and -44.05 kJ mol-1 for VOLph, CuLph, and H2Lph, respectively, due to the central metal ion (VIVO and CuII ions). VOLph (with a higher oxidation state of the V4+ ion and oxo-ligand) exhibited enhanced interaction with the ctDNA molecule compared to CuLph, demonstrating the role and type of the central metal ion within the performed electronegative and electrophilic characters.

EDB-FN Targeted Peptide-Drug Conjugates for Use against Prostate Cancer.

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can differentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buffered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 h. Confocal microscopy studies demonstrated increased binding of ligand 8 to EDB-FN compared to ligand 1. Therefore, we hypothesized that the EDB-FN targeted peptides (1 and 8) conjugated with an anticancer drug via a hydrolyzable linker would provide selective cytotoxicity to the cancer cells. To test our hypothesis, we selected both the normal prostate cell line, RWPE-1, and the cancerous prostate cell lines, PC3, DU-145, LNCaP, and C4-2, to evaluate the anticancer activity of synthesized peptide-drug conjugates. Docetaxel (Doce) and doxorubicin (Dox) were used as anticancer drugs. Dox conjugate 13 containing disulfide linkage showed comparable cytotoxicity versus Dox after 72 h incubation in all the cancer cell lines, whereas it was found to be less cytotoxic on RWPE-1, suggesting that it can act as a Dox prodrug. Doce conjugate 14 was found to be less cytotoxic in all the cell lines as compared to drug alone.

Synthesis and Biological Evaluation of 2-Aminobenzothiazole and Benzimidazole Analogs Based on the Clathrodin Structure.

A series of 2-aminobenzothiazole and benzimidazole analogs based on the clathrodin scaffold was synthesized and investigated for their antimicrobial and antiproliferative activities as well as for their effects in hepatitis C virus (HCV) replicon model. Compound 7, derived from 2-aminobenzothiazole, exhibited moderate antimicrobial activity only against the Gram-positive bacterium, Enterococcus faecalis. In the antiviral assay, compounds 4d and 7 were found to suppress the HCV replicon by >70%, but also to exhibit cytotoxicity against the host cells (35 and 44%, respectively). Compounds 4a and 7 demonstrated good activity in the antiproliferative assays on the human melanoma cell line A-375. To assess the selectivity of the effects between cancerous and noncancerous cells, a mouse fibroblast cell line was used. The IC50 values for compound 7 against the melanoma cell line A-375 and the fibroblast cell line BALB/c 3T3 were 16 and 71 µM, respectively, yielding fourfold selectivity toward the cancer cell line. These results suggest that compound 7 should be studied further in order to fully explore its potential for drug development.

Photocatalytic, antiproliferative and antimicrobial properties of copper nanoparticles synthesized using Manilkara zapota leaf extract: A photodynamic approach.

Copper nanoparticles were synthesized using Manilkara zapota leaf extract. The synthesis of the nanoparticle was primarily visualized when the colour of the reaction mixture turned into reddish-brown. Biosynthesized nanoparticles were characterized by UV-vis, FT-IR, XRD, SEM and EDX. The UV spectra showed maximum absorption at 584 nm. FT-IR studies showed stretching frequency at 592.76 cm-1, which is the fingerprint region for Cu-O bond. The crystallinity of the synthesized copper nanoparticles (Mz-Cu NPs) was revealed through XRD analysis. The synthesized Mz-Cu NPs were spherical with an average size of 18.9-42.5 nm and it was shown by SEM analysis. EDX analysis displayed that the nano sample contains 58 % of copper. The antimicrobial property of the synthesized nanoparticles was evaluated against fungal plant pathogens Rhizoctonia solani (MTCC 12232), Sclerotium oryzae (MTCC 12230) and bacterial species, namely Bacillus subtilis (ATCC 23857), Escherichia coli (ATCC 25922), Staphylococcus aureus (ATCC 25923), Vibrio harveyi (ATCC 35084), Vibrio parahaemolyticus (ATCC 33845). In in-vitro haemolytic assay, the particle showed 5.73, 3.34, 0.5 % hemolysis at 100, 50, 25 µg/mL concentration respectively. In the antiproliferative assay, the IC50 values of MCF7 and Vero cells were found to be 53.89 and 883.69 µg/µl. The particle degraded Methyl violet, Malachite green and Coomassie brilliant blue by 92.2, 94.9 and 78.8 %, within 50, 40 and 60 min, respectively, through its photocatalytic activity.

In vitro treatment of Toxoplasma gondii with copper(II) complexes induces apoptosis-like and cellular division alterations.

Toxoplasma gondii is the causative agent of toxoplasmosis, which is one of the most common parasitic diseases in the world. This pathogen causes severe damage to immunocompromised hosts, and the most frequently used therapy is the combination of pyrimethamine and sulfadiazine, which has side effects. Thus, there is a need for new therapies that target T. gondii. Herein, we present the anti-Toxoplasma effect of two new copper(II) complexes: [(H2L1) Cu (µ-Cl)2 Cu(H2L1)] Cl2·5H2O (1) and [(H2L2) Cu (µ-Cl)2 Cu(H2L2)] Cl2·6H2O (2). Complexes (1) and (2) irreversibly controlled parasite growth in vitro, with IC50 values of 0.78µM and 3.57µM, respectively, after 48h. These complexes induced part of the tachyzoite population to convert to bradyzoites, which eventually die. The cell death mechanism was unknown, but signs of apoptosis, such as membrane blebs and nuclear fragmentation, and necrosis, such as plasma membrane disruption, intense cytoplasm vesiculation and the release of cellular contents, were seen. In addition, complex (2) interfered with the correct disposition of the inner membrane complex of the parasite, affecting cell division. These results indicate that these copper complexes have potential effects against T. gondii and may be used as drugs in the future or serve as prototypes for the development of new drugs to treat toxoplasmosis.

Composition and antiproliferative effect of essential oil of Origanum vulgare against tumor cell lines.

Cancer is a leading cause of death and is responsible for one in eight deaths worldwide. The use of herbs as complementary medicine for cancer, especially advanced cancer, has recently increased. The aim of this study was to evaluate in vitro, the antiproliferative effect of Origanum vulgare against human breast adenocarcinoma (MCF-7), and human colon adenocarcinoma (HT-29). The essential oil (EO) was extracted from a bought amount of O. vulgare dried leaves and analyzed in a gas chromatograph interfaced with a mass selective detector. The cytotoxicity test was performed by sulforhodamine B assay. The results show that the EO is composed mostly of 4-terpineol and induces a high cytotoxicity effect in HT-29. In the MCF-7 cell line the EO was less effective. In conclusion, this study showed that O. vulgare main component is 4-terpineol and was effective in inducing cancer cell growth inhibition.