A selective CuII complex with 4-fluorophenoxyacetic acid hydrazide and phenanthroline displays DNA-cleaving and pro-apoptotic properties in cancer cells

The thin line between efficacy and toxicity has challenged cancer therapy. As copper is an essential micronutrient and is important to tumor biology, CuII complexes emerged as an alternative to chemotherapy; however, its biological properties need to be better understood. Thus, we report in vitro the antitumor effects of two CuII complexes named [Cu(4-fh)(phen)(ClO4)2] (complex 1) and [Cu(4-nh)(phen)(ClO4)2]·H2O (complex 2), in which 4-fh = 4-fluorophenoxyacetic acid hydrazide; 4-nh = 4-nitrobenzoic hydrazide and phen = 1,10-phenanthroline. Both complexes presented cytotoxic activity against tumor cells, but only complex 1 showed significant selectivity. Complex 1 also induced DNA-damage, led to G0/G1 arrest and triggered apoptosis, which was initiated by an autophagy dysfunction. The significant in vitro selectivity and the action mechanism of complex 1 are noteworthy and reveal this prodrug as promising for anticancer therapy.

Green synthesis, characterization, biological evaluation and docking study of some pyrazoline and pyrimidine derivatives

Green and classical techniques have been utilized for preparing of a variety of aryl - substituted pyrazoline and pyrimidine derivatives (2-8). Reactions of chalcones 1 with semicarbazide and thiosemicarbazide, nicotinic acid hydrazide and amino guanidine hydrochloride afforded the corresponding N-substituted pyrazoline derivatives 2-5. Pyrimidine derivatives 6-8 were achieved via reaction of chalcone derivatives 1 with several reagents namely: guanidine nitrate, thiourea and 6-amino-2-thioxo-2,3- dihydropyrimidin-4(1H)-one under conventional and ultrasonic conditions. Ultrasonic method was found to be an easy work-up procedure and it gave high yield in comparison with conventional method. The structures of new synthesis compounds were characterized by elemental and spectral analyses. Some of newly compounds were tested in vitro antibacterial activity against some gram–positive and gram–negative. The antimicrobial results displayed favorable antimicrobial activity. Molecular docking has been perfomed for compound 5b using MOE 2008.10, The data results obtained are quite promising.

Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a–3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N′-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

Genotypic and phenotypic diversity of Mycobacterium tuberculosis complex genotypes prevalent in West Africa

Findings from previous comparative genomics studies of the Mycobacterium tuberculosis complex (MTBC) suggest genomic variation among the genotypes may have phenotypic implications. We investigated the diversity in the phenotypic profiles of the main prevalent MTBC genotypes in West Africa. Thirty-six whole genome sequenced drug susceptible MTBC isolates belonging to lineages 4, 5 and 6 were included in this study. The isolates were phenotypically characterized for urease activity, tween hydrolysis, Thiophen-2-Carboxylic Acid Hydrazide (TCH) susceptibility, nitric oxide production, and growth rate in both liquid (7H9) and solid media (7H11 and Löwenstein–Jensen (L-J)). Lineage 4 isolates showed the highest growth rate in both liquid (p = 0.0003) and on solid (L-J) media supplemented with glycerol (p<0.001) or pyruvate (p = 0.005). L6 isolates optimally utilized pyruvate compared to glycerol (p<0.001), whereas L5 isolates grew similarly on both media (p = 0.05). Lineage 4 isolates showed the lowest average time to positivity (TTP) (p = 0.01; Average TTP: L4 = 15days, L5 = 16.7days, L6 = 29.7days) and the highest logCFU/mL (p = 0.04; average logCFU/mL L4 = 5.9, L5 = 5.0, L6 = 4.4) on 7H11 supplemented with glycerol, but there was no significant difference in growth on 7H11 supplemented with pyruvate (p = 0.23). The highest release of nitrite was recorded for L5 isolates, followed by L4 and L6 isolates. However, the reverse was observed in the urease activity for the lineages. All isolates tested were resistant to TCH except for one L6 isolate. Comparative genomic analyses revealed several mutations that might explain the diverse phenotypic profiles of these isolates. Our findings showed significant phenotypic diversity among the MTBC lineages used for this study.

Green Synthesized Silver Nanoparticles as Potent Antifungal Agent against Aspergillus terreus Thom

Medicinal plants are composed of a rich pool of biomolecules and have been increasingly recognized for their antimicrobial properties; however, increasing concerns have been put on the bioavailability features. Thus, this study is aimed at exploring the synthesis and characterization of silver nanoparticles synthesized by Chenopodium album L. leaf extract and assessing the antifungal activity against Aspergillus terreus Thom. Plant extract was prepared in methanol to synthetize silver nanoparticles, which were then characterized by Scanning Electron Microscopy (SEM), UV-Visible spectroscopy, and particle size analysis. UV-Visible analysis indicated maximum absorption at 378 nm, and an average particle size was observed as 25.6 nm. Oval to hexagonal shape was observed by SEM. Antifungal activity of silver nanoparticles (1, 1.5, 2, 2.5, 3, and 3.5%) was addressed against A. terreus biomass. At 3.5%, silver nanoparticles revealed to be highly effective, leading to 92% retardation in fungus growth. In next phase, various organic fractions, viz., chloroform, n-butanol, n-hexane, and ethyl acetate, were obtained from plant methanol extract, and the corresponding silver nanoparticles were prepared. These fractions were also assessed for antifungal activity, and n-hexane fraction led to 64% inhibition in A. terreus biomass. Following gas chromatography-mass spectrometry (GC-MS), 18 compounds were identified, namely, 1,3-cyclopentadiene-5-(1 methylethylidene and o-xylene), ethyl benzene, octadecane, nonane, decane, 2-methylheptane, n-hexadecane, 2-methylheptane, and eicosane, along with carbonyl compounds (4,4-dimethyl-3-hexanone) and phenols, like stearic acid, propionic acid hydrazide, and 2,4-di-T-butylphenol. These findings proved that C. album silver nanoparticles are highly effective against A. terreus.

Insilico Design and Synthesis, Evaluation of Anti-Colon Cancer Activity of Novel Stilbene Hybrids

Various biologically important Stilbene analogues were competently synthesized using inexpensive, non-toxic, and readily available amino acids and Stilbene; the systematic study was carried out to characterize parameters such as TLC, melting point, IR, 1H NMR and mass spectral studies. The synthesized compounds were screened for anticancer activities. The molecular docking studies have been performed by using software Autodock 4.2, Autodock vina. The targeted proteins are P450a2 & Estrogen. The reaction of phenylacetic acid substituted Benzaldehyde, and triethylamine in acetic anhydride was irradiated in a microwave oven for 3 minutes at 700W afforded (2E)-3-(substituted phenyl)-2-phenylacrylic acid. The above compound, after irradiating with hydrazine provided (2E)-3-(substituted phenyl)-2-phenyl acrylic acid hydrazide. Anti-Cancer activity for synthesized compounds was evaluated using the MTT assay technique against colon cancer. The results were obtained as a percentage in cell lysis data. The IC50 value of the compounds was between 0.037-0.0257 µM/lt. Among all the compounds, tyrosine derivatives exhibited the more potent activity. Insilico studies PCB-arg having more binding affinity with the receptor Cytochrome P450 A2 and PCB-try having more binding affinity with the receptor estrogen beta when compared to other derivatives.