Facile Synthesis and in Vitro Cytotoxic Evaluation of Novel Thiadiazole,Pyrazole, and Dithiole-Androstane Derivatives

In the aim of identifying new steroidal cytotoxic agents with potential antiproliferative activity against hepatoma cell lines (Hep-G₂), we synthesized modified steroids containing the thiadiazole, pyrazole, or dithiole moiety. Epiandrosterone 1 reacted with carbon disulfide and sodium hydride to furnish α-oxoketene dithio-disodium salt 2. Treatment of 2 with the hydrazonoyl halides 5a–d produced the thiadiazole anellated androstanone 7a–d, respectively. The reaction of 1 with hydrazine hydrate produced the hydrazide adduct 8, which cyclized upon reflux in acetic acid to form the condensed pyrazoloandrostanone derivative 9. Interaction of 8 with carbon disulfide and sodium hydride formed the disodium salt 10, which reacted with ethylchloroacetate to furnish the final adduct, dithioloandrostane derivative, 13. Compounds 7a, 7d, 9, and 13 were examined for their cytotoxicity against a panel of hepatoma cell lines (Hep-G₂) using MTT assay. The results provide that, at incubation time 72 h, in DMSO, compound 7d (50 μ mol/mL) showed the most significant cytotoxic effect at P < 0.05. The higher dose (100 μ mol/mL) of compound 7d, at 48 h incubation, reversed the effect causing resistance and the growth rate return to the control level.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Bigger data,collaborative tools and the future of predictive drug discovery

Over the past decade we have seen a growth in the provision of chemistry data and cheminformatics tools as either free websites or software as a service commercial offerings. These have transformed how we find molecule-related data and use such tools in our research. There have also been efforts to improve collaboration between researchers either openly or through secure transactions using commercial tools. A major challenge in the future will be how such databases and software approaches handle larger amounts of data as it accumulates from high throughput screening and enables the user to draw insights, enable predictions and move projects forward. We now discuss how information from some drug discovery datasets can be made more accessible and how privacy of data should not overwhelm the desire to share it at an appropriate time with collaborators. We also discuss additional software tools that could be made available and provide our thoughts on the future of predictive drug discovery in this age of big data. We use some examples from our own research on neglected diseases, collaborations, mobile apps and algorithm development to illustrate these ideas.     

Structural properties of the trimetallic acetylide complex [{Ru(CO)2(η5C5H5)}3(η1:η1:η2:-CC)]+

The purpose of this Note is the study of the structure and fluxional behavior of the complex [{Ru(CO)₂(η⁵C₅H₅)}₃(η¹:η¹:η²:-CC)]⁺, using density functional methods. The molecular geometry of this complex will be optimized, the transition state (TS) of the fluxional process will be determined and the origin of the energy barrier will be analyzed.     

Electrochemical characterization and stress corrosion cracking behavior of α-brass in molybdate-containing electrolytes

One of the major challenges in material design is the achievement of reasonable operational efficiency through understanding the factors affecting the material’s performance particularly strength and service lifetime characteristics. In this work, the electrochemical behavior of 72Cu–28Zn α-brass alloy in Na₂MoO₄-containing electrolytes was investigated using potentiodynamic polarization and electrochemical frequency modulation techniques complemented with scanning electron microscopy. Also, stress corrosion cracking behavior of the alloy under both open-circuit potential and anodic applied potentials, using the slow strain rate technique, was evaluated. The results drawn from the different techniques are comparable.     

Biological Effect,Aquation, and Kinetics of Oxidation of Bis(2‐aminobenzothiazole)dichlorocobalt(II) Complex by Periodate in Aqueous Acidic Medium

The biological effect, aquation, and kinetics of oxidation of bis(2‐aminobenzothiazole)dichlorocobalt(II) complex by periodate in aqueous acidic solutions were studied. The complex exhibited a broad resistance toward the studied pathogens. The average value of the aquation constant was calculated spectrophotometrically as 2.55 × 10^?5 mol² dm^?6. Kinetics of the oxidation reaction showed first‐order dependence on each reactant concentration and increased by increasing pH over the 3.80–4.80 range, 35–50°C, and decreased by increasing the ionic strength over the 0.1–0.5 mol dm^?3 range. The polymerization of acrylonitrile was taken as an evidence for an inner‐sphere mechanism through the formation of free radical intermediates of Co(III) complexes, which were slowly converted to the final Co(III)products.     

Synthesis and anticancer activity of some new heterocyclic compounds based on 1-cyanoacetyl-3,5-dimethylpyrazole

Research on Chemical Intermediates - The starting 3-(3,5-dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrile (1) reacts with phenyl isothiocyanate and ethyl bromoacetate to give the corresponding...     

Strategic analysis of the dairy transportation problem

The dairy transportation problem (DTP) consists of determining the best routes to be performed for collecting milk from farms and delivering it to processing plants. We study the particular case of the province of Quebec, where the Fédération des producteurs de lait du Québec is responsible for negotiating the transportation costs on behalf of producers. Several issues are highlighted in the actual process of designing contracts such as using historical data. We propose an approach based on scenario analysis that consists of revising both the steps and the information used to construct the routes. We develop a generalized tabu search algorithm that integrates the different characteristics of the DTP.     

Synthesis,spectroscopic characterization,thermal behaviour,in vitro antimicrobial and anticancer activities of novel ruthenium tricarbonyl complexes containing monodentate V‐shaped Schiff bases

The interaction of Ru₃(CO)₁₂ with a novel family of monodentate V‐shaped Schiff base ligands (L^1–4; L¹: (E)‐1‐(4‐((4‐bromobenzylidene)amino)phenyl)ethanone, L²: (E)‐1‐(3‐(4‐(dimethylamino)benzylideneamino)phenyl)ethanone, L³: (E)‐1‐(4‐(4‐(dimethylamino)benzylideneamino)phenyl)ethanone, L⁴: (E)‐1‐(3‐(3,4‐dimethoxybenzylideneamino)phenyl)ethanone) in air under atmospheric pressure afforded the novel complexes [Ru(CO)₃(L^1–4)₂]. The parent ligands and their complexes were characterized using elemental analyses and spectroscopic techniques. In addition, the structure of the representative ligand L¹ was determined using single‐crystal X‐ray analysis. The stereochemistry and theoretical optimization of the three‐dimensional geometry of the ligands and their complexes were justified. In vitro antimicrobial screening against bacterial stains Escherichia coli and Staphylococcus aureus and fungus Candida albicans was conducted. Cytotoxicity of the compounds as anti‐tumour agents was evaluated against liver carcinoma (HepG2), breast carcinoma (MCF7) and colon carcinoma (HCT‐116) cell lines relative to cisplatin and doxorubicin. The complexes showed variable in vitro cytotoxic activities against the three studied cell lines, with IC₅₀ values less than those of cis‐platin, and thus appear to be building blocks for promising anti‐tumour agents.     

Divalent manganese,cobalt, copper and cadmium complexes of (Z)‐N‐benzoyl‐N′‐(1H‐1,2,4‐triazol‐3‐yl)carbamimidothioic acid: Preparation,characterization, computational and biological studies

In this work, (Z)‐N‐benzoyl‐N′‐(1H‐1,2,4‐triazol‐3‐yl)carbamimidothioic acid and its Mn(II), Co(II), Cu(II) and Cd(II) complexes were introduced for the first time. This carbonyl thiourea ligand was prepared by the reaction of 1H‐1,2,4‐triazol‐3‐amine with benzoyl isothiocyanate. The structural elucidation of these compounds was performed using elemental analysis and spectral and magnetic measurements. Octahedral structures of all complexes, except Cd(II) complex with a tetrahedral geometry, were confirmed by applying DFT structural optimization. The thermal decomposition behaviour of metal complexes of carbonyl thiourea ligand is discussed. The calculation of kinetic parameters for prepared complexes (E_a, A, ΔH*, ΔS* and ΔG*) of all thermal degradation stages has been evaluated using two comparable approaches. Antimicrobial and ABTS‐antioxidant studies indicated potent activity of Cd(II) complex compared with the other investigated compounds. The cytotoxic activity of the prepared compounds was investigated in vitro. The results indicated potent activity of Mn(II) complex against both HePG2 (liver carcinoma) and MCF‐7 (breast carcinoma) cancer cells.