No abstract

All-atom molecular dynamics (MD) simulation combined with Markov state model (MSM) were used to uncover the structural characteristics and misfolding mechanism of the key R3 fragment of tau protein at the atomic level.

The role played by organic chemistry in the pharmaceutical industry continues to be one of the main drives in the drug discovery process. More than ever, the industry demands from organic chemists the development of small molecules, which could be a rich source of biological potential. In this context, a diverse range of quinoline-4-carboxylic acid derivatives has been synthesized and evaluated as potent inhibitors of alkaline phosphatases. The structural build-up

A series of isonicotinohydrazide derivatives was synthesized and tested against recombinant human and rat ecto-5'-nucleotidases (h-e5'NT and r-e5'NT) and alkaline phosphatase isozymes including both bovine tissue-non-specific alkaline phosphatase (b-TNAP) and tissue-specific calf intestinal alkaline phosphatase (c-IAP). These enzymes are implicated in vascular calcifications, hypophosphatasia, solid tumors, and cancers, such as colon, lung, breast, pancreas, and ovary. All tested compounds were active against both enzymes. The most potent inhibitor of h-e5'NT was derivative (E)-N'-(1-(3-(4-fluorophenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)ethylidene)isonicotinohydrazide (3j), whereas derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) exhibited significant inhibitory activity against r-e5'NT. In addition, the derivative (E)-N'-(4'-chlorobenzylidene)isonicotinohydrazide (3a) was most potent inhibitor against calf intestinal alkaline phosphatase and the derivative (E)-N'-(4-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (3g) was found to be most potent inhibitor of bovine tissue-non-specific alkaline phosphatase. Furthermore, putative binding modes of potent compounds against e5'NT (human and rat e5'NT) and AP (including b-TNAP and c-IAP) were determined computationally.

No abstract

Background and purposeIn developing countries like Pakistan the cost effectiveness and patient convenience in any treatment modality is a question of major concern. The purpose of this study was two-fold; first to report our experience with a high-dose rate Iridium-192 surface mould brachytherapy of keloid scars after surgical excision, using different radiation treatment regimen and second to establish the most convenient and cost effective treatment protocol having no compromise on the treatment outcomes.Materials and methodsFrom January 2012 to April 2015 a total 51 patients with 65 keloid lesions underwent postoperative Iridium-192 high-dose rate surface mould brachytherapy. The dose regimen used was: 8 Gy in a single fraction, 10 Gy in a single fraction, 15 Gy in three fractions and 18 Gy in three fractions. The median follow-up period was 33 months (range 15–53 months).ResultsThe success rates were 57·2, 89·5, 85 and 89·5% for the treatment regimen of 8 Gy/F×1, 10 Gy/F×1, 5 Gy/F×3 and 6 Gy/F×3, respectively. Grade 2 or above radiation induced toxicity was not observed.FindingsThe results of this study show that a dose regimen of 10 Gy (biological effective dose=20 Gy) in a single fraction have comparable results with a dose regimen of 15 Gy in three fractions or 18 Gy in three fractions. 10 Gy in a single fraction is therefore the most convenient and cost effective dose regimen for the management of keloid scars in developing countries like Pakistan, while 8 Gy in a single fraction is considered suboptimal and discouraged in practice.

A series of novel pyrazole–rhodanine derivatives was designed, synthesized, and biologically evaluated for their potential inhibitory effect on both aldehyde reductase (ALR1) and aldose reductase (ALR2).

No abstract