Pt(IV) Complexes in the Search for Novel Platinum Prodrugs with Promising Activity.

The kinetically inert, six coordinated, octahedral Pt(IV) complexes are termed dual-, triple-, or multi-action prodrugs based on the nature of the axially substituted ligands. These ligands are either inert or biologically active, where the nature of these axial ligands provides additional stability, synergistic biological activity or cell-targeting ability. There are many literature reports from each of these classes, mentioning the varied nature of these axial ligands. The ligands comprise drug molecules such as chlorambucil, doxorubicin, valproic acid, ethacrynic acid, biologically active chalcone, coumarin, combretastatin, non-steroidal anti-inflammatory drugs (NSAIDs) and many more, potentiating the anti-proliferative profile or reducing the side effects associated with cisplatin therapy. The targeting and non-targeting nature of these moieties exert additive or synergistic effects on the anti-cancer activity of Pt(II) moieties. Herein, we discuss the effects of these axially oriented ligands and the changes in the non-leaving am(m)ine groups and in the leaving groups on the biological activity. In this review, we have presented the latest developments in the field of Pt(IV) complexes that display promising activity with a reduced resistance profile. We have discussed the structure activity relationship (SAR) and the effects of the ligands on the biological activity of Pt(IV) complexes with cisplatin, oxaliplatin, carboplatin and the Pt core other than approved drugs. This literature work will help researchers to get an idea about Pt(IV) complexes that have been classified based on the aspects of their biological activity.

Risk Factors and Hazards in the Household Environment for Elevated Blood Lead Levels in Urban Preschool Children of Vellore: A Case-Control Approach in the MAL-ED Birth Cohort.

OBJECTIVES: To study the household environmental risk factors and hazards associated with elevated blood lead levels (EBLLs) in preschool children in an urban setting of Vellore, South India. METHODS: A case-control study within the MAL-ED (Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development) birth cohort was conducted between January 2014 and January 2015. The study included 153 pre-school children: 87 cases and 66 controls with elevated and normal BLLs, respectively. A structured questionnaire was used to assess the sociodemographic profile, household environment, breastfeeding practices, children's habits, and the use of cosmetics in them. Household environmental samples of wall and door paint, floor dust, drinking water, and cosmetics were estimated for lead levels using gas flame atomic absorption spectrometry (FAAS). RESULTS: Children born with low birth weight, those living in houses painted at least once in the last five years and those residing in houses older than ten years had a higher odds of EBLLs [OR (95% CI) = 3.79 (1.24-11.1); 4.84 (1.42-16.53); 5.07 (2.06-12.46), and 2.58 (0.99-6.69)], respectively. Drinking water samples from both cases (88%) and controls (95%) had lead levels more than the Environmental Protection Agency (EPA), USA recommendation of 0.015 ppm. CONCLUSIONS: Low birth weight and the household environment pose important risk factors/hazards for elevated blood lead levels in urban preschool children. Multipronged interventions that include government legislations, household environmental modification, safe water supply, and community education are pivotal in reducing lead exposure in young children.

Ultrasonication-Assisted and Benzimidazolium-Based Brønsted Acid Ionic Liquid-Catalyzed Transesterification of Castor Oil.

In this investigation, we report the synthesis of biodiesel using benzimidazolium-based brønsted acid ionic liquid (BBAIL) catalyst under the influence of ultrasonication. The prepared BBAIL catalyst was characterized by Fourier transform infrared and NMR spectroscopy techniques, and its acidity was determined by the Hammett method with 4-nitroaniline as the indicator. Ultrasonicator horn (22 kHz, 500 W) was used in this work with an on-off cycle of 50-20 s at 70% amplitude. The highest biodiesel yield of 96% was achieved by ultrasonication when 1:10 molar ratio of castor oil to methyl alcohol was used at 50 °C temperature with 9 mol % of the catalyst in just 90 min, which is about 10 times lesser than the process without ultrasonication. At similar conditions, 96% biodiesel yield was obtained in 14 h without ultrasonication. In summary, ultrasonication proved to be an efficient way to improve biodiesel synthesis in less time and BBAIL showed excellent activity toward the conversion of glycerides to synthesize biodiesel. Other important highlights are easy separation of the catalyst and recyclability up to three cycles with small decrease in its activity.

A bioinspired ionic liquid tagged cobalt-salophen complex for nonenzymatic detection of glucose.

The development of efficient and cost effective nonenzymatic biosensors with remarkable sensitivity, selectivity and stability for the detection of biomolecules, especially glucose is one of the major challenges in materials- and electrochemistry. Herein, we report the design and preparation of nonenzymatic biosensor based on an ionic liquid tagged cobalt-salophen metal complex (Co-salophen-IL) immobilized on electrochemically reduced graphene oxide (ERGO) for the detection of glucose via an electrochemical oxidation. The bioinspired Co-salophen-IL complex has been synthesized and immobilized on ERGO, which was previously deposited on a screen printed carbon electrode (SPE) to form the Co-salophen-IL/ERGO/SPE nonenzymatic biosensor. The electrochemical behaviour of this modified electrode was studied using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). Notably, the Co-salophen-IL/ERGO/SPE biosensor exhibited excellent electrocatalytic activity towards glucose oxidation in 0.1M NaOH, based on which an amperometric sensor has been developed. The modified electrode has shown prominent performance towards glucose detection over a wide linear range from 0.2µM to 1.8mM with a detection limit and sensitivity of 0.79µM and 62µAmM-1 respectively. The detection was carried out at 0.40V and such a less working potential excludes the interference from the coexisting oxidizable analytes. The role of Co-salophen, IL and ERGO in the electrocatalytic activity has been systematically investigated. Furthermore, the biosensor demonstrated high stability with good reproducibility.

Recent developments of metal N-heterocyclic carbenes as anticancer agents.

Metal based anticancer drugs have demonstrated their crucial role in preventing all types of cancers whereas their effectiveness is selective with respect to the cancer cells rather than the normal cells. Recently metal N-heterocyclic carbenes have established their selective performance for cancer cells excluding normal healthy cells based on which they are widely utilised for targeting cancer cells specifically which leads to cell death or cell growth inhibition. This is mainly due to their ionic character which helps them to localise in cancer cells with the help of enhanced expression of Organic Cation Transporters (OCT). Also their unique mechanism of action involving DNA binding, less recognizable by DNA repair machinery, mitochondria targeting gives them a new area for anticancer drug development. This review summarises the medicinal as well as pharmacological approach to the anticancer properties of metal NHC complexes.

Synthesis and evaluation of cyclohexane carboxylic acid head group containing isoxazole and thiazole analogs as DGAT1 inhibitors.

Diacylglycerol acyltransferase 1 (DGAT1) is known to play an important catalytic role in the final step of triglyceride biosynthesis. High fat diet fed DGAT1 knockout mice were resistant to weight gain and exhibited increased insulin and leptin sensitivity thereby indicating a plausible role for DGAT1 inhibitors in the treatment of obesity. 4-Phenylpiperidine-1-carbonyl cyclohexanecarboxylic acid (compound 6, DGAT1 IC50 = 57 nM) has been lately reported as a potent DGAT1 inhibitor. In our search for newer scaffolds possessing potent DGAT1 activity we undertook a systematic diversification of compound 6 to identify a 4-(5-phenylthiazole-2-carboxamido)cyclohexanecarboxylic acid scaffold. Further linker optimization of this scaffold identified compound 9e (DGAT1 IC50 = 14.8 nM) as a potent DGAT1 inhibitor. Coupled with its in vitro potency, compound 9e also exhibited 112 percent plasma triglyceride reduction at a 3 mpk dose in an oral fat tolerance test (FTT) when studied in Swiss mice.